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Del Rio D, Stewart AJ, Pellegrini N. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 15, 316-328

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Del Rio D, Stewart AJ, Pellegrini N. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 15, 316-328

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Abstract

Of the many biological targets of oxidative stress, lipids are the most involved class of biomolecules. Lipid oxidation gives rise to a number of secondary products. Malondialdehyde (MDA) is the principal and most studied product of polyunsaturated fatty acid peroxidation. This aldehyde is a highly toxic molecule and should be considered as more than just a marker of lipid peroxidation. Its interaction with DNA and proteins has often been referred to as potentially mutagenic and atherogenic. This review is intended to briefly describe the physiological origin of MDA, to highlight its toxicity, describe and comment on the most recent methods of detection and discuss its occurrence and significance in pathology. In vivo origin as well as reactivity and consequent toxicity of MDA are reviewed. The most recent and improved procedures for the evaluation of MDA in biological fluids are described and discussed. The evidence of the occurrence of increased MDA levels in pathology is described. In the assessment of MDA, the most common methods of detection are insufficiently sensitive and disturbed by interference coming from related species or overestimation derived from stressing analysis conditions. Moreover, no recent nutritional or medical trials report the use of one of the new and more reliable methods, some of which are undoubtedly accessible to virtually all the laboratories provided with a common HPLC or a spectrofluorimeter.

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... As a result, the vulnerability of the brain regions to oxidative damage was reduced after Naringenin administration. In addition, lipid peroxidation (LPO) is a recognized sign of oxidative stress brought on by excessive ROS and low antioxidant levels, which is how cellular lipids are oxidized [30]. A byproduct of lipid peroxidation called malondialdehyde (MDA) is regarded as a reliable diagnostic of increasing lipid peroxidation and a sign of tissue damage [30]. ...
... In addition, lipid peroxidation (LPO) is a recognized sign of oxidative stress brought on by excessive ROS and low antioxidant levels, which is how cellular lipids are oxidized [30]. A byproduct of lipid peroxidation called malondialdehyde (MDA) is regarded as a reliable diagnostic of increasing lipid peroxidation and a sign of tissue damage [30]. An increase in MDA level was observed in animals treated with Imipenem/Cilastatin, however, data from this study further showed that the increased level of MDA in the rats was attenuated by Naringenin. ...
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Imipenem/Cilastatin are antibiotics that are used to treat a variety of bacterial infections. In clinical practice, Imipenem is co-administered with Cilastatin to prevent post-renal metabolism of Imipenem, and the use of these two has attracted some level of toxicity, whereas Naringenin, a flavonoid with various biological activities, has also been demonstrated as a potent antioxidant with a strong inhibitory effect on free radicals. This study was designed to evaluate the attenuation of naringenin on Imipenem/Cilastatin-induced neurotoxicity in rats. Twenty-four Wistar rats were randomly compartmentalized into four groups of six rats each. Group A (Control) received distilled water; group B received naringenin (50 mg/kg) orally, group C received Naringenin (50mg/kg) orally and Imipenem/Cilastatin (100 mg/kg) intraperitoneally, group D received Imipenem/Cilastatin (100 mg/kg) intraperitoneally. Some biomarkers of oxidative stress and inflammation were assessed. Imipenem/Cilastatin caused a significant increase (P < 0.05) of nitric oxide (NO), malonaldehyde (MDA) levels, myeloperoxidase (MPO) activities, followed by a decrease in ascorbic acid, reduced glutathione (GSH) levels, glutathione-S-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities relative to control in the cerebellum, cerebrum, hippocampus sections of the brain. However, co-administration of Naringenin with Imipenem/Cilastatin ameliorated the aforementioned alterations as Naringenin is suggested to offer protection against oxidative stress induced by Imipenem/Cilastatin in rats by scavenging free radicals.
... However, P. lunatus was hardly affected in this respect. MDA is considered a suitable biomarker for directly evaluating cellular oxidative stress as it is a reactive aldehyde generated by increased free-radical production [22]; no significant increase in MDA was found in most cases, only for the Pintat landrace in the maximum water stress condition. Conversely, common bean revealed an augment of MDA levels under water stress even in tolerant genotypes [24,29,67,71,72]. ...
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Agrobiodiversity and adaptability to environmental changes derived from global warming are challenges for the future of agriculture. In this sense, landraces often have high levels of genetic variation, tightly connected with the changing environmental conditions of a territory. The genus Phaseolus, with five domesticated species, is one of the most important sources of proteins, carbohydrates and micronutrients in various countries. This study aimed to compare the adaptation capacity to drought, in the vegetative growth phase, of a commercial cultivar and two landraces traditionally cultivated in the Mediterranean basin of Phaseolus lunatus (Lima bean). Growth and biochemical responses of the analysed genotypes to different water-deficit treatments were evaluated and compared. In addition, the effectiveness of the voltammetric method for evaluating stress levels in cultivated plants was tested. The studied parameters revealed that P. lunatus is a drought-tolerant species, showing similar results for the three cultivars. However, contrary to what was expected from the germination phase results, the commercial variety Peru showed some better responses under water stress conditions. Finally, the voltammetric method proved to be a good and fast tool for assessing oxidative stress in cultivated plants, showing results in agreement with total phenolic compounds and total flavonoid fluctuations.
... In contrast, increased oxygen demands by active muscles due to acute exercise leads to increased oxygen consumption and mitochondrial activity, which consequently induces OS by increasing the production of reactive oxygen species, such as the superoxide radical (O 2˙− ) [12,22]. Lipids have been proposed as the most relevant biomolecule among the various biological targets of OS [23]. Both 4-HNE and MDA reflect lipid peroxidation and have been reported as one of the blood indicators of exercise-induced OS [14,24,25]. ...
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Exercise can induce anti-inflammatory and antioxidant effects, for which regulation of sirtuins (SIRTs) may be a major consideration for exercise prescription. The purpose of this study was to investigate the effects of acute aerobic exercise, in particular its intensity, on systemic oxidative stress, inflammatory responses, and SIRT levels. Twenty healthy, untrained males were recruited and randomly assigned to moderate-intensity (MI, 65% VO2max, n = 10) and high-intensity (HI, 85% VO2max, n = 10) exercise. Blood samples were obtained pre-, immediately post-, and 1 h post-exercise for measurements of malonaldehyde (MDA), superoxide dis-mutase (SOD), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, SIRT-1, SIRT-2, and SIRT-3. Overall, MDA, SOD, IL-6, SIRT-1, and SIRT-3 levels were significantly increased at post-exercise compared with pre-exercise regardless of exercise intensity (p < 0.05). The HI group had significantly higher MDA, SOD, and IL-6 levels than the MI group at post-exercise (p < 0.05), whereas no significant differences were observed in the IL-1β, TNF-α, and SIRT-2 levels (p > 0.05). Altogether, these findings suggest that exercise-induced oxidative stress and inflammatory responses may be dependent on exercise intensity. Moreover, activation of inflammatory cytokines and SIRT family members may be dependent on the intensity of the exercise.
... During oxidative stress, malondialdehyde (MDA) is a key product of lipid peroxidation following the action of reactive oxygen species (ROS), and thus serves as a useful marker of oxidative stress (Del Rio et al. 2005), such as in research related to human diseases (Paliogiannis et al. 2018) or plant abiotic and biotic stresses (Alch e 2019). ...
Article
Malondialdehyde (MDA) is a product of lipid peroxidation that is often determined in abiotic stress-related phytoremediation research. This study assessed (July 14, 2022) the frequency of eight nomenclatural forms of MDA between 2001 and 2021 using three major databases (PubMed, Scopus, and Web of Science (WoS9). The most common form (75,060, 57,874, and 65,663 times in PubMed, Scopus, and WoS, respectively) of MDA was “malondialdehyde”, followed by “malonaldehyde” (68,240, 3815, and 2337 times in these three databases, respectively). According to WoS, the journals that used “malondialdehyde” and “malonaldehyde” most frequently were Environmental Science and Pollution Research (Springer-Nature) (587 times) and The Journal of Chemical Physics (AIP Publishing) (57 times). Other less-frequent forms were: malonyldialdehyde, malonic dialdehyde, malon-dialdehyde, malone dialdehyde, malonic aldehyde, and malonodialdehyde. We recommend that the editors of journals that publish papers with themes that are closely associated with plant stress specify in their instructions for authors their journal’s preferable nomenclatural form of MDA. The plant abiotic stress community, including phytoremediation specialists, need to debate this topic with the objective of seeking a standardized nomenclatural form of MDA, which would help to fortify the integrity of searches in major databases by allowing all relevant literature to be accurately identified. Novelty statement Malondialdehyde (MDA), a product of lipid peroxidation that is often determined in stress-related phytoremediation research, has various forms to its name. These nomenclatural variations were assessed in PubMed-, Scopus-, and Web of Science-indexed literature. This is the first study to detect, report, quantify and debate these forms of MDA.
... Increased levels of the lipid peroxidation product MDA play a very important role in the pathogenesis of various diseases. [3] Currently, research dedicated to the psychobehavioral modulation of immune function called psychoneuroimmunology have shown the stress-induced immune impairment. [4] The immune dysfunction leads to inflammation and damages cell turning to for lipid peroxidation. ...
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When oxidant compounds target lipids, they can initiate the lipid peroxidation process, a chain reaction that produces multiple breakdown molecules, such as Malondialdehyde (MDA). Psychological stress is reported to induce enhancement of lipid peroxidation in the brain. Objective: The present study was therefore planned to evaluate whether there is increase in oxidative stress in medical students undergoing examination induced psychological stress. Materials and Method: Institutional Ethics Committee permission and seventy nine students of either sex between the age group 19 to 21 years. Students studying in first year of medical college were recruited in the study. All students signed the written informed consent before collecting blood samples. 5 ml of blood was collected from each student in a plain vaccutainer just before appearing for viva examination. Serum was separated immediately by centrifugation and MDA was estimated using (TBA) thiobarbituric acid method. Result: We observed that in 24 individuals lipid peroxidation was higher (>3 nmol/ml) than normal level (0‑3 nmol/ml). The number of female students showing higher values of MDA was higher than male students with similar values of MDA (p<0.05). Conclusion: Our study thus highlights the relation between lipid peroxidation and psychological stress and also the sex wise difference in the stress levels. Keywords: Lipid peroxidation, malondialdehyde, reactive oxygen species, stress
... MDA is a product of lipid peroxidation of cell membranes and is one of the general biomarkers of oxidative damage (Sim et al., 2003;Kadiiska et al., 2005). According to Del Rio et al. (2005) and Russo & Bracarense (2016), MDA is both genotoxic and cytotoxic and has deleterious interaction with DNA and proteins of the host. The presence of many prognosticators has made detections of patients at high risk of death and their subsequent planned management more encouraging and successful (Schoeman et al., 2013). ...
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Canine parvovirus is a deadly virus affecting the Canid family, causing virus-induced destruction of rapidly dividing haemopoietic precursor cells such as crypts of intestinal epithelial cells, thymus, lymph nodes, bone marrow precursor cells, blood cells and cardiac cells leading to multi-organ dysfunctions. The aim of this study was to determine the haematological, serum biochemical and electrolytic changes associated with canine parvovirus (CPV) -2 infection. An immunochromatographic test was used to differentiate the virus-positive and negative dogs using faecal samples. One hundred and sixty whole blood and serum samples were collected from apparently healthy and CPV-2-positive dogs in Plateau State, Nigeria. Haematological, serum biochemical and electrolytic analyses were done using standard methods. The data obtained were analyzed using descriptive statistics and a student t-test. Significance was accepted at probability values of p < 0.05. The haematological effect of CPV-2 showed a significant (P < 0.05) decrease in mean Packed Cell Volume (PCV), total red blood cell count, haemoglobin concentration, total white blood cell count, neutrophils, lymphocytes and platelet count. In addition, the CPV-2 significantly (P < 0.05) increased the mean aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, urea, creatinine, triglyceride and malondialdehyde, while the mean total protein, sodium, potassium, chloride and cholesterol significantly (P < 0.05) decreased in the infected dogs. From the findings, CPV infection variably and significantly affected some haematological and serum biochemical parameters of infected dogs. Therefore, clinicians should endeavour to incorporate haematinics, haptatonics and immunemodulators during the management of canine parvoviral infection as supportive drugs with fluid therapy to improve the survivability of infected animals.
... In addition, MDA can react with deoxyadenosine and deoxyguanosine in DNA to form DNA adducts, thus increasing the probability of mutations (Marnett, 1999). Therefore, MDA can be used as a biomarker to measure the level of oxidative stress in an organism (De Rio et al., 2005). Our results indicated that P. megacephalus tadpoles can suffer significant oxidative stress after long-term exposure to a relatively high TPhP concentration. ...
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The toxicity of triphenyl phosphate (TPhP) to aquatic organisms in surface waters has been demonstrated; However, an understanding of toxicity profiles of TPhP in amphibians is limited. Therefore, the adverse effects and threshold concentrations of TPhP on metamorphosis, growth, locomotion, and hepatic antioxidants of Gosner stage 25 Polypedates megacephalus tadpoles under long-term (35 d) exposure to six TPhP concentrations until complete metamorphosis were assessed. Additionally, the overall effect of using integrated multiple biomarkers were determined to demonstrate the potential ecological risks of waterborne TPhP at environmentally relevant concentrations in amphibian tadpoles. With increasing TPhP concentrations, physical parameters (snout-vent length, body mass, condition factor, and hepatic somatic index), jumping distance, hepatic catalase, and superoxide dismutase activities decreased, whereas metamorphosis time and malondialdehyde content increased. The threshold concentration of TPhP that affected the tadpole biomarker, except for metamorphosis rate and jumping distance, was 50–400 μg/L. Furthermore, the standardized scores of the examined integrated biomarkers in the six TPhP concentrations were visualized using radar plots and calculated as the integrated biomarker responses (IBRs). The varying TPhP concentrations had different scores in the radar plots, and the threshold for affecting the IBR value was 10 μg/L, which was close to the TPhP concentration in surface waters. Additionally, IBR values were strongly positively correlated with the TPhP concentrations. These findings indicate that environmentally relevant exposure to waterborne TPhP can pose an ecological risk to amphibian tadpoles. This study can serve as a reference and assist in the formulation of relevant policies and strategies to control TPhP pollution in water bodies.
... Similarly, Fig. 10b shows the p-anisidine index, which represents the secondary lipid oxidation products associated with polyunsaturated fatty acid oxidation [61]. The ...
Article
This work investigates the stability of high internal phase emulsions (HIPEs) made from 75% (w/w) soybean oil and 25% lentil protein isolate dispersion (LPI concentration of 2, 4, and 6%, w/w) at pH 3 and 7. Soybean oil is rich in polyunsaturated fatty acids (linoleic and oleic), and lentil protein is rich in essential amino acids such as lysine and leucine. The LPI dispersions were characterized by SDS-PAGE, intrinsic fluorescence, zeta potential measurement, solubility determination, particle size distribution, and differential scanning calorimetry. The HIPEs were characterized for oil loss after centrifugation, droplet size distribution, morphology, rheology, Turbiscan stability index, and lipid oxidation over 60 days of storage at 25 °C. HIPEs containing 4 and 6% LPI presented lower values of droplet size distribution (31.70±0.00 µm and 35.57±0.00 µm at pH 3, and 18.55±0.97 µm and 16.53±0.86 µm at pH 7, respectively) and oil loss (2.61±0.33 and 1.90±0.67 at pH 3, 1.80±0.14% and 1.40±0.50% at pH 7, respectively). These HIPEs showed elastic behavior, creamy visual appearance, and better stability than HIPEs with lower LPI concentrations. These results show that HIPEs can be stabilized solely with LPI at concentrations of 4 and 6% at pH 3 and 7. In addition, these HIPEs can be used as a potential substitute for saturated fat in foods.
... As rehearsed above, and in much more detail previously [15,106], while peroxide and superoxide are intermediates, and at high levels are cytotoxic, it is also the hydroxyl radical that causes many or most of the manifestations of oxidative stress and, in particular, of ischaemia-reperfusion injury. Because it is so reactive, it is not observable directly; however, the products of the effective reaction of ROSs with proteins (nitrotyrosine [563][564][565][566][567]), lipids (malondialdehyde [568,569]), and DNA (8-oxoguanine [570][571][572][573][574]) are. Consequently, if we wish to know that I-R injury is a contributor to the kinds of syndromes we are discussing here, we 'simply' need to check whether they manifest these oxidative biomarkers. ...
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Ischaemia-reperfusion (I-R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety of acute circumstances. We argue here that I-R injury also underpins elements of the pathology of a variety of chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be initiated via fibrin amyloid microclot blockage of capillaries, for instance as exercise is started; reperfusion is a necessary corollary when it finishes. We rehearse the mechanistic evidence for these occurrences here, in terms of their manifestation as oxidative stress, hyperinflammation, mast cell activation, the production of marker metabolites and related activities. Such microclot-based phenomena can explain both the breathlessness/fatigue and the post-exertional malaise that may be observed in these conditions, as well as many other observables. The recognition of these processes implies, mechanistically, that therapeutic benefit is potentially to be had from antioxidants, from anti-inflammatories, from iron chelators, and via suitable, safe fibrinolytics, and/or anti-clotting agents. We review the considerable existing evidence that is consistent with this, and with the biochemical mechanisms involved.
... [21] It has been observed that oxidative stress induces many diabetic complications, including coronary artery disease, neuropathy, nephropathy, retinopathy and stroke. [17] Biomarkers of oxidative stress include malondialdehyde (MDA) (polyunsaturated fatty acid peroxidation and hence considered a meaningful sign of lipid peroxide) and [22] catalase (CAT) (a vital component of the antioxidant defence system that supports each other and provides a protective defence against ROS). [23] One of the primary antioxidant cellular defence systems is the hexose monophosphate (HMP) pathway. ...
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Objectives Type 2 diabetes mellitus (T2DM) is a complex disease that affects many organs. Oxidative stress plays a key role in the pathogenesis of insulin resistance and β-cell dysfunction. Thus, the present study aimed to use oxidative stress markers as early predictors for the progression of diabetic complications. Materials and Methods The study sample included 400 individuals (300 T2DM and 100 non-diabetic controls) aged from 35 to 59 years randomly selected from the outpatient clinic of the National Institute for Diabetes and Endocrinology. T2DM patients were divided into subgroups: Subgroup (1) patients without any complications, Subgroup (2) patients with diabetic nephropathy (DN) and Subgroup (3) patients with cardiovascular disorders (CVD). Biochemical markers of fasting blood glucose, glycated haemoglobin (HbA1C), glucose-6-phosphate dehydrogenase (G6PD), lactate, arginase, heme oxygenase-1 (HO-1), haemoglobin (Hb), triglycerides (TG), cholesterol, low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), urea, creatinine, malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT) and nitric oxide (NO) were performed. Results DM patients showed significant increases in body mass index, systolic blood pressure, diastolic blood pressure, FBS, HbA1C, cholesterol, TG, LDL-C and glomerular filtration rate, while HDL-C decreased. Significant increases were observed in HO-1, MDA and NO, while G6PD/lactate, GSH and CAT decreased in DM patients. The DN and CVD patients exhibited a significant increase in HO-1, MDA and NO; while G6PD/lactate, GSH and CAT decreased compared with DM patients. Receiver operating characteristic analysis showed that the sensitivity and specificity of oxidative stress markers were 66.67–100%. Conclusion Hexose monophosphate (HMP)/glycolysis pathways are shifted during DM near glycolysis rather than HMP pathway to produce energy where the amount of glucose enters the cells is low, causing oxidative stress. Oxidative stress markers could be used as early predictors of diabetes complications.
... In addition, studies have shown that BDE-209 can cause liver injury, and the degree of liver tissue and function injury in T2DM patients can be reflected by detecting the activity of ALT and AST (Ali et al. 2018). MDA is one of the products of lipid peroxidation in cells, which levels can reflect the state of oxidative stress and oxidative damage of the body (Del Rio et al. 2005). It has been reported that exposure to BDE-209 could elevate the activities of AST and ALT in hippocampal neurons, which was harmful to the liver (Chen et al. 2022). ...
Article
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Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance (IR) and has attracted worldwide attention due to its high prevalence. As a typical persistent organic pollutant, decabromodiphenyl ether (BDE-209) has been detected in food and human samples, and the concentration trends increase year by year. In addition, it has been proved to have the potential to increase the risk of IR, but it is rarely reported whether it could aggravate IR in T2DM. Therefore, in this study, the IR-BRL (buffalo rat liver cells with IR) model was applied to study the metabolism toxicity and susceptibility of BDE-209. Results showed that BDE-209 could inhibit glucose absorption and increase the levels of serum total cholesterol (TC) and triglyceride (TG), ultimately leading to the disorder of glucolipid metabolism in IR-BRL cells. Besides, it also could cause cell damage by increasing the levels of aspartate transaminase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) in cells. Moreover, its potential mechanisms were to: (1) affect the transport of glucose, synthesis of glycogen and fatty acid via IRS-1/GLUT4 and IRS-1/PI3K/AKT/GSK-3β pathways; (2) impact the proliferation and differentiation by regulating the expression of Mek1/2, Erk1/2, and mTOR proteins and genes. Furthermore, susceptibility analysis showed that there was a significant synergism interaction between IR and BDE-209, which suggested that IR-BRL cells were more susceptible to the metabolism toxicity induced by BDE-209.
... The results of Hoseinifar et al. [91] showed that activity of CAT, growth rate, and GST was significantly increased in prebiotic, probiotic, and synbiotic groups compared with the control in Oncorhynchus mykiss. MDA level is considered to be suitable indicator of the extent of lipid peroxidation [92]. A decrease of MDA level can be considered as an increase of antioxidants of defense mechanisms [93]. ...
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The present study investigated the effects of combined and singular oral administration of Bio-Aqua® with different dosages of sodium diformate (NaDF) on biochemical indices, innate immune responses, antioxidant effects, and expressions of immunological related genes of Caspian brown trout (Salmo trutta caspius). Fingerlings Salmo trutta caspius (n = 1800; initial weight 15 ± 3 g) were randomly allocated into five groups (120 fish group-1 in triplicates). Control diet: without any addition, G1, G2, G3, and G4 received diets containing 0.2 g kg−1 commercial probiotic Bio-Aqua® combined with 0, 0.5, 1.0, and 1.5% NaDF to the basal diet for 60 days according to recommended dosages reported in previous studies. Results indicated that serum bactericidal activity (G3 on day 60 and G1 on day 30) and classic complement in all groups (on day 60) (G1 and G2 on day 30) were significantly elevated (P < 0.05). The serum lysozyme, glucose, globulin, and albumin levels showed no significant differences between all groups compared to the control group (P > 0.05). On days 30 and 60 of the sampling, no significant difference was observed in the amount of superoxide disotase (SOD) and catalase (CAT) between the treatments (P > 0.05) but activity of malondialdehyde (MDA) was lower in G1 than the control (P < 0.05). The expression of the immune-regulating genes IL-10, IL-1β, GTP, FATP, and IGF was significantly improved in all probiotic + acidifier–treated groups (P < 0.05). The current findings showed that mixture of Bio-Aqua® and NaDF (1.5% + pro) is beneficial, as it effectively improves some immune parameters and expression of immunological and growth-related genes in Caspian brown trout.
... DAG is a lipid mediator that promotes upregulation of the apoptotic and profibrotic pathways in addition to the production of reactive oxygen species (ROS) (Volpe et al. 2018). On the other hand, MDA is a lipid peroxidation product which is widely used as a marker of oxidative stress (Del Rio et al. 2005). Notably, it has been previously reported that dexamethasone can cause cardiac dysfunction by the activation of angiotensin II pathway and the induction of myocardial lipid peroxidation (Qi and Rodrigues 2007). ...
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The current study aimed to investigate the cardiotoxic effect of dexamethasone-high-dose in rats, the therapeutic effect of carvedilol and the role of α1-adrenergic receptor (α1AR). The experiment involved 6 groups: control, dexamethasone (10 mg/kg), carvedilol (10 mg/kg), phenylephrine (1 mg/kg), phenylephrine plus carvedilol and propranolol (30 mg/kg). Drugs and vehicles were given for 7 days. Dexamethasone was given with the drugs in the last 4 groups. On the 8 th -day and after overnight fasting, serum and cardiac samples were collected. Serum levels of cardiac troponin I and creatine kinase–myoglobin as well as cardiac levels of diacylglycerol, malondialdehyde, kinase activity of Akt, transforming growth factor-β, Smad3 and alpha smooth muscle actin were measured. Cardiac samples were also used for histopathological examination using hematoxylin–eosin and Sirius red stains, in addition to immunohistochemical examination using β-arrestin2 antibody. Dexamethasone induced cardiac injury via increasing oxidative stress, apoptosis and profibrotic signals. Carvedilol significantly reduced the dexamethasone-induced cardiotoxicity. Using phenylephrine, a competitive α1-agonist, with carvedilol potentiated the cardioprotective actions of carvedilol. Propranolol, a β-blocker without activity on α1ARs, showed higher cardiac protection than carvedilol. Dexamethasone-high-dose upregulates cardiac oxidative stress, apoptotic and profibrotic signals and induces cardiac injury. Blocking the α1-adrenergic receptor by carvedilol attenuates its cardioprotective effects against dexamethasone-induced cardiotoxicity.
... Each value represents the mean ± SD. (a) significant compared with group I (Negative control), (b) significant compared with group II (Positive control) Lipid peroxides, calculated as MDA, are widely used as one of the most effective oxidative stress indices to assess oxidative damage in patients with liver injury[42][43][44]. Increased levels of MDA contribute to the pathogenesis of several metabolic diseases including cancer[45] ...
Article
Nanoparticles can be synthesized by chemical, physical and biological system methods. In this work, Superparamagnetic Iron Oxide@Silver nanoparticles (SPION@Ag NPs) were modified by zinc oxide nanoparticles (ZnO NPs). SPION@Ag core shell NPs were synthesized by the biological method using Fusarium oxysporum fungus and coated with ZnO NPs. This method is eco-friendly and low cost. Characterization techniques such as UV, FTIR, HR-TEM, HR-SEM, XRD and zeta potential were used. The most common type of liver cancer is hepatocellular carcinoma (HCC). Hepatocellular carcinoma was induced by a single dose of diethyl nitrosamine (DEN) 60 mg/Kg b.wt. and was followed after two days by carbon tetra chloride (CCl 4) diluted with paraffin oil (50% v/v, 2 ml/Kg b.wt.) twice a week for one month. A histopathological examination was done after sacrifying. Clear changes were shown in the comparison between the HCC group treated with ZnO@SPION@Ag nanocomposite and the positive control group. Liver function tests showed a highly significant decrease after using the nanocomposite for HCC treatment. Our study aim is to evaluate the therapeutic anticancer effect of ZnO@SPION@Ag nanocomposite on hepatocellular carcinoma in male albino rats, which was synthesized by a new method called green chemistry or green synthesis.
... As a result, changes in antioxidant enzymes would alter the cellular redox homeostasis. Malondialdehyde (MDA) is the best investigated product of lipid peroxidation induced by oxidative stress [40], it could be served as an indirect indicator of ROS level. Then the content of MDA was measured, and it was lower in IL85 root tips than that in B73 (Fig. 7D) as expected, which may explain part of the different REC between IL85 and B73 under cold stress (Fig. 1B). ...
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Background As maize originated in tropical or subtropical zones, most maize germplasm is extremely sensitive to low temperatures during the seedling stage. Clarifying the molecular mechanism of cold acclimation would facilitate the breeding of cold tolerant maize varieties, which is one of the major sustainability factors for crop production. To meet this goal, we investigated two maize inbred lines with contrasting levels of cold tolerance at the seedling stage (IL85, a cold tolerant line; B73, a cold sensitive line), and performed full-length transcriptome sequencing on the root tips of seedlings before and after 24 h of cold treatment. Results We identified 152,263 transcripts, including 20,993 novel transcripts, and determined per-transcript expression levels. A total of 1,475 transcripts were specifically up-regulated in the cold tolerant line IL85 under cold stress. GO enrichment analysis revealed that 25 transcripts were involved in reactive oxygen species (ROS) metabolic processes and 15 transcripts were related to the response to heat. Eight genes showed specific differential alternative splicing (DAS) in IL85 under cold stress, and were mainly involved in amine metabolism. A total of 1,111 lncRNAs were further identified, 62 of which were up-regulated in IL85 or B73 under cold stress, and their corresponding target genes were enriched in protein phosphorylation. Conclusions These results provide new insights into the molecular mechanism of cold acclimation during the seedling stage in maize, and will facilitate the development of cultivars with improved cold stress tolerance.
... Recent studies have suggested that hyperoxia induces pro-inflammatory cytokines and cell infiltration in the alveolar spaces in neonatal Sprague Dawley rats [52]. MDA is the main product of lipid peroxidation and is recognized as a biological marker of oxygen stress injury [53,54]. In this study, rats reared in hyperoxia exhibited a significant increase in BALF protein content, as well as TNF-α, IL-1β, IL-6, MIP-1α, MIP-1β, MPO, and MDA levels, which decreased with hUC-MSC treatment. ...
Article
Background: Bronchopulmonary dysplasia (BPD) is not merely a chronic lung disease, but a systemic condition with multiple organs implications predominantly associated with hyperoxia exposure. Despite advances in current management strategies, limited progress has been made in reducing the BPD-related systemic damage. Meanwhile, although the protective effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) or their exosomes on hyperoxia-induced lung injury have been explored by many researchers, the underlying mechanism has not been addressed in detail, and few studies have focused on the therapeutic effect on systemic multiple organ injury. Aim: To investigate whether hUC-MSC intratracheal administration could attenuate hyperoxia-induced lung, heart, and kidney injuries and the underlying regulatory mechanisms. Methods: Neonatal rats were exposed to hyperoxia (80% O2), treated with hUC-MSCs intratracheal (iT) or intraperitoneal (iP) on postnatal day 7, and harvested on postnatal day 21. The tissue sections of the lung, heart, and kidney were analyzed morphometrically. Protein contents of the bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) expression, and malondialdehyde (MDA) levels were examined. Pulmonary inflammatory cytokines were measured via enzyme-linked immunosorbent assay. A comparative transcriptomic analysis of differentially expressed genes (DEGs) in lung tissue was conducted via RNA-sequencing. Subsequently, we performed reverse transcription-quantitative polymerase chain reaction and western blot analysis to explore the expression of target mRNA and proteins related to inflammatory and oxidative responses. Results: iT hUC-MSCs administration improved pulmonary alveolarization and angiogenesis (P < 0.01, P < 0.01, P < 0.001, and P < 0.05 for mean linear intercept, septal counts, vascular medial thickness index, and microvessel density respectively). Meanwhile, treatment with hUC-MSCs iT ame liorated right ventricular hypertrophy (for Fulton's index, P < 0.01), and relieved reduced nephrogenic zone width (P < 0.01) and glomerular diameter (P < 0.001) in kidneys. Among the beneficial effects, a reduction of BALF protein, MPO, and MDA was observed in hUC-MSCs groups (P < 0.01, P < 0.001, and P < 0.05 respectively). Increased pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-1β, and IL-6 expression observed in the hyperoxia group were significantly attenuated by hUC-MSCs administration (P < 0.01, P < 0.001, and P < 0.05 respectively). In addition, we observed an increase in anti-inflammatory cytokine IL-10 expression in rats that received hUC-MSCs iT compared with rats reared in hyperoxia (P < 0.05). Tran scriptomic analysis showed that the DEGs in lung tissues induced by hyperoxia were enriched in pathways related to inflammatory responses, epithelial cell proliferation, and vasculature development. hUC-MSCs administration blunted these hyperoxia-induced dysregulated genes and resulted in a shift in the gene expression pattern toward the normoxia group. hUC-MSCs increased heme oxygenase-1 (HO-1), JAK2, and STAT3 expression, and their phosphorylation in the lung, heart, and kidney (P < 0.05). Remarkably, no significant difference was observed between the iT and iP administration. Conclusion: iT hUC-MSCs administration ameliorates hyperoxia-induced lung, heart, and kidney injuries by activating HO-1 expression and JAK/STAT signaling. The therapeutic benefits of local iT and iP administration are equivalent.
... Diabetes-induced tissue/cellular injury is often accompanied by an imbalance in the generation of ROS and the production of antioxidant enzymes (Sayed, 2012). These observations agree with an earlier report on oxidative stress occurring due to diabetes (Del Rio, Stewart, & Pellegrini, 2005); and reversing this imbalance could attenuate diabetes-induced tissue damage (Shoorei et al., 2020). The recovered MDA levels of the diabetic treated rats (especially in the liver and kidney homogenates) indicate that the amino acid(s) regimen attenuated lipid peroxidation and suppressed oxidative stress. ...
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We evaluated the effects of supplementation of L‐alanine and L‐glutamine on blood glucose levels and biochemical parameters in alloxan‐induced diabetic rat. Forty‐nine animals were distributed into seven equal groups. Except for the non‐diabetic control, diabetes was induced in all groups by intravenous alloxan injection followed by daily supplementation with amino acids for 14 days. Weight and blood glucose were monitored during supplementation, while biochemical parameters such as liver and renal functions, lipid profile, and antioxidant markers were evaluated post‐intervention. A significant increase (p < .05) in weight and decrease in blood glucose were observed in the amino acid(s) treated groups. The supplementation with both amino acids restored important tissue antioxidants, liver and kidney functions and rescued islets cells degeneration. Histopathological examinations of important tissues showed the restoration of alloxan‐induced physiopathological changes by the amino acids. Thus, these amino acids might serve as nutraceuticals for the management and treatment of diabetes. Practical Applications The discovery and production of antidiabetic bioactive compounds are often challenging, and the existing antidiabetic drugs are expensive. Amino acids are key regulators of glucose metabolism, insulin secretion, and insulin sensitivity; thus, they can play a crucial role in alleviating diabetes. Here, we present findings that strongly suggest the potential of pure amino acids (L‐alanine and L‐glutamine) for the management and treatment of diabetes. We show that these amino acids, when supplemented singly or coadministered can lower blood glucose levels and restore several other biochemical parameters implicated in diabetes. Hence, these cheap amino acids may be consumed as nutraceuticals or food supplements by diabetics for the treatment/management of diabetes. Foods rich in these amino acids may also be consumed as part of the diet of diabetic patients.
... Oxidative stress is known as the most important guilt in chronic diseases. Oxidative stress results from an elevation of oxidants with concomitant reduction in antioxidants [53]. Dietary antioxidants exert their effects through elimination of reactive oxygen species and subsequently prevent the activation of the inflammatory process [54]. ...
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Purpose of Review Chronic diseases are problematic to health professional specially when using drugs throughout the course of life with un-tolerated side effects. Returning to nature through using nutraceuticals might have both protective and therapeutic effects. Date palm was claimed to be a good source of such nutraceuticals or functional food ingredients. The purpose of the present review was to spot light on the different phytochemicals, phytonutrients, and remedial effects of date palm (Phoenix dactylifera L.) in a goal to be utilized in form of nutraceuticals. The possible mechanisms of action of the remedial effects were among the aim of the study. Recent Findings A protein hydrolyzate prepared from date seed could prevent DNA mutation and susceptibility to cancer. In addition to cancer prevention, date palm fruit improved the treatment outcome of cancer pediatric patients and possesses anti-angiogenic activity as one of the important anticancer mechanisms of action. On the other hand, date seed extracts was recently reported to protect from ulcerative colitis. It seems that all the aforementioned remedial effect might be ascribed to immunoregulatory effect of date palm. These findings proposed that date palm is beneficial for health. Summary Date palm fruit is a rich source of vitamins, minerals, dietary fibers, energy, and easily digestible and absorbable sugars that instantaneously replenish and revitalize the body specially after fasting condition. Mineral contents in date fruits include potassium, phosphorus, magnesium, and calcium. Diverse health claims were reported to belong to various parts of the tree including the edible part of fruits, the seeds, the leaves, spathe (an envelope-like structure that encloses male and female date palm flowers), and pollen grains due to the presence of different bioactive constituents. The main phytochemicals and phytonutrients reported in date palms are phenolic compounds, carotenoids, sterols, anthocyanins, and others. In folk medicine, date palm fruits are used for enhancing immunity and treating gastrointestinal tract disorders, edema, bronchitis, wound, cancer, as well as infectious diseases. However, the exact health benefits and remedial effects of date palm were not fully and deeply investigated. The present review focused on the bioactive constituents and the reported health benefits of date palm and proposed mechanism of action.
... When we looked at the MDA values, it was found to be quite high in the fluorine-applied group. It is known that MDA is a lipid peroxidation marker, it causes intracellular ion imbalance, and disruption of enzyme activities and leads to changes in the structure of DNA (27,28). In a study conducted on rabbits, it was reported that fluorine poisoning caused kidney damage, a decrease in the levels of SOD, GSH-Px, CAT, GSH-Rd, and an increase in the level of MDA (29). ...
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Aim: The aim of this study is to investigate the effects of chitosan application on lung tissue in rats with experimental fluorine toxicity. Material and Method: In the study, 21 healthy male wistar albino rats were used. Prior to the trial, the acclimation of the rats was provided. 3 groups were randomly generated in a way that there were 7 rats in each group. These were determined as the control group (C), the fluorosis group (NaF) and the fluorosis + chitosan (NaF+CS) group. Results: In the NaF group, CAT, SOD and GSH values were found to be low compared to other groups and MDA values were found to be high. It was found that the chitosan application reduced the CAT, SOD and GSH values, and increased the MDA value. Conclusion: It has been predicted that chitosan application may be beneficial in preventing cellular damage that may occur with fluorine exposure.
... MDA is determined indirectly, by measuring a substance that reacts with thiobarbituric acid (TBARS) in plasma. It is a highly toxic molecule, and its interaction with DNA and proteins can be mutagenic and atherogenic (15)(16)(17). ...
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Introduction. Obesity represents a public health problem and within women in labor, it affects not only the mother and the pregnancy but also the health of the fetus. Maternal overweight and obesity in pregnancy are factors that cause metabolic changes in the newborn, including elevated levels of oxidative stress (OS). The aim of the study was to determine the association between maternal body mass index (BMI) and oxidative stress marker levels in their newborns. Methods. A prospective study included 150 mothers and their healthy newborns who were divided into three groups according to progestational BMI. Maternal and umbilical cord blood samples were collected immediately after delivery. Triglycerides and Thiobarbituric Acid Reactive Substances (TBARS) levels were quantified. Results. Triglyceride levels were significantly higher in obese mothers and their newborns compared to overweight and normal weight mothers. Significantly elevated levels of TBARS have been observed in obese mothers and their newborns. Maternal BMI was significantly positively correlated with TBARS in mothers (r = 0.290; P = 0.000) and in newborns (r = 0.387; P = 0.000). Maternal (r = 0.540; P = 0.000) and neonatal triglycerides levels (r = 0.483; P = 0.000) were significantly positively associated with BMI. Conclusion. The values of oxidative stress markers TBARS and triglycerides in mothers and newborns immediately after birth were significantly higher in the obese mothers group.
... MDA, a toxic by-product and one of the biomarkers of OS [98,99], is the most studied product of polyunsaturated fatty acid (PUFA) peroxidation [100]. Our results showed that the most severe lipid-peroxidation-mediated oxidative damages were found in the serum/plasma and erythrocyte membranes of AD patients compared to that in control subjects, which was in agreement with the increased MDA levels observed in the 60-day alcohol-fed albino Wistar rats [79]. ...
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Alcohol-induced oxidative stress (OS) plays a pivotal role in the pathophysiology of alcohol dependence (AD). This meta-analysis was aimed at investigating the changes in the levels of OS biomarkers in AD patients. We included relevant literature published before 1 April 2022, from the PubMed, Web of Science, and EBSCO databases following PRISMA guidelines. Finally, 15 eligible articles were enrolled in this meta-analysis, including 860 patients and 849 controls. Compared with healthy controls, AD patients had lower activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes, and lower levels of albumin, while levels of malondialdehyde (MDA), vitamin B12, homocysteine, and bilirubin were significantly increased in serum/plasma samples of AD subjects (all p < 0.05). In male patients, the activities of SOD and GPx were increased in serum/plasma but decreased in erythrocytes (all p < 0.05). The opposite trends in the level of SOD and GPx activities in serum/plasma and erythrocytes of male patients could be used as the biomarker of alcohol-induced OS injury, and the synergistic changes of MDA, vitamin B12, albumin, bilirubin, and homocysteine levels should also be considered.
... Commonly measured markers include measures of lipid peroxidation, such as F2a-isoprostanes (isoP) and malondialdehyde (MDA). MDA is currently regarded as a general biomarker of oxidative damage in the plasma (Kadiiska et al. 2005) and Del Rio et al. (2005) inferred that MDA is highly cytotoxic and genotoxic, and should be considered more than just a biomarker of oxidative damage, owing to its interaction with DNA and other proteins. The methods most widely used now a days to detect the action of ROS indirectly, include either measuring the products generated from its action on biomolecules or measuring the quality and quantity of antioxidants, thereby evaluating oxidative damage (Mak, 2008). ...
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The present study was carried out to evaluate biomarkers of oxidative stress and antioxidant activity in female dogs undergoing laparoscopic and open elective ovariectomy at Bihar Veterinary College, Patna in 2016-17. Twenty healthy animals were randomly divided into four groups A, B, C and D consisting of 5 animals each. The ovariectomy was performed through laparoscopy in group A and group B. Open elective ovariectomy procedure was used in group C and group D. Evaluation of surgical techniques have been done on the basis of biomarkers for oxidative stress and antioxidant activity at Pre, Post and 4 th day post surgery. The superoxide dismutase value on day 4 th in group B showed significant difference with highest value followed by groups A, C and D respectively. The catalase values on day 4 th in group B were significantly different from groups A and D but not significantly different from group C. The values within the groups showed significant higher values on day 4 th as compared to pre and post intervals of time. It was concluded that less oxidative stress is induced during surgical procedure by laparoscopy as compared to open laparotomy ovariectomy in canines.
... The result was similar to the study in Nile tilapia (Yu et al. 2016(Yu et al. , 2020a. MDA is the biomarker of oxidative damage (Del et al. 2005). In the present study, MDA content in larvae fed diets with 20 and 40 mg/kg FA was significantly decreased compared to the control group, suggesting that FA reduced the oxidative damage of large yellow croaker larvae. ...
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A 30-day feeding trial was conducted to investigate the effects of supplemental ferulic acid (FA) on survival, growth performance, digestive enzyme activities, antioxidant capacity and lipid metabolism of the large yellow croaker larvae (initial weight: 2.58 ± 0.30 mg). Four isonitrogenous and isolipidic micro-diets were formulated with graded levels of FA (0, 20, 40, and 80 mg/kg) and fed to the experimental larvae seven times daily. Results showed that larvae fed the diet with 40 mg/kg FA had significantly higher survival rate, while the specific growth rate was higher in larvae fed diets with 40 and 80 mg/kg FA than the control group (P < 0.05). Activities of trypsin in pancreatic segments (PS) and intestinal segments, lipase in PS and alkaline phosphatase in brush border membrane were significantly increased by supplementation of FA compared to the control group (P < 0.05). Supplementation of FA significantly increased activities of total superoxide dismutase and catalase, and reduced the malondialdehyde content compared to the control group (P < 0.05). Meanwhile, activities of lysozyme, total nitric oxide synthase and nitric oxide content were significantly improved by supplemental FA in diets. Furthermore, supplementation of 40 mg/kg FA reduced the triglyceride content in larval visceral mass probably through down-regulating expression of lipogenesis-related genes (scd1, fas and dgat2) and up-regulating expression of lipid catabolism-related genes (aco, cpt-1 and hl). In conclusion, appropriate supplementation of 40 mg/kg FA could improve the survival and growth performance of large yellow croaker larvae through increasing digestive function, antioxidant capacity and promoting lipid metabolism.
... Among them, SOD, a key antioxidant enzyme, is capable of eliminating cellular superoxide anion radicals by converting them to less harmful hydrogen peroxide, which could be further decomposed by CAT or GSH-Px (Sies et al., 2017). The GSH, the most abundant cellular nonprotein thiol antioxidant, serves as a main intracellular redox buffer (Lu, 2013), while MDA is one of the final products of cellular lipid peroxidation (Del Rio et al., 2015). The BS administration linearly or quadratically reduced 14-d serum and 21-d hepatic MDA concentration, and increased serum GSH-Px and CAT activities at 14 and 21 days as well as 14day hepatic CAT activity. ...
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This study was designed to examine the effects of different levels of beta-sitosterol (BS) supplementation on growth performance, serum biochemical indices, redox status, and intestinal permeability-related parameters and morphology of young broilers. Two hundred and forty male Arbor Acres broiler chicks were allocated into five groups of six replicates with eight birds each, and fed a basal diet supplemented with 0, 25, 50, 75, and 100 mg/kg BS for 21-days, respectively. The BS quadratically decreased feed conversion ratio during 1 to 14 days and 1 to 21 days, with its effect being more prominent at 25 or 50 mg/kg (P < 0.05). The BS linearly and quadratically reduced 14-day plasma diamine oxidase activity and D-lactate level, and this effect was more pronounced when its supplemental level was 25 or 50 mg/kg (P < 0.05). The BS linearly increased duodenal villus height (VH) and quadratically increased jejunal VH and ratio of VH and crypt depth (CD) at 14 days, and these effects in 25 mg/kg group were more remarkable (P < 0.05). Similarly, BS linearly or quadratically increased VH and ratio of VH and CD, but decreased CD in the jejunum and ileum at 21 days, with these effects being more pronounced at 50 mg/kg (P < 0.05). The BS supplementation especially at 50 or 75 mg/kg linearly or quadratically reduced 14-day serum and 21-day hepatic malondialdehyde concentration, and increased serum glutathione peroxidase and catalase activities at 14 and 21 days (P < 0.05). Moreover, the BS administration linearly and/or quadratically increased glutathione peroxidase, catalase, and superoxide dismutase activities and glutathione level, and reduced malondialdehyde accumulation in the intestinal mucosa at 14 and/or 21 days, and these consequences were more significant in 50 to 100 mg/kg BS-supplemented groups (P < 0.05). The results demonstrated that BS administration could improve growth performance, intestinal barrier function, and antioxidant status of broilers at an early age, with these effects being more pronounced at a level of 50 mg/kg.
Article
A bioanalytical technique for quantitative determination of MDA by HPLC-MS/MS. The proposed method for determining MDA includes the release stage of bound MDA and excludes the derivatization reaction. The lower limit of quantitative detection was 600 nmol/l, the volume of the required sample was 10 µl, the analysis time was 7 min. The range of concentrations obtained during the study makes it possible to use this bioanalytical technique to determine the concentration of MDA in biological material when assessing physiological and pathological conditions.
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Spinal cord injury (SCI) is a serious central nervous system disease, and secondary injury, including oxidative stress, the inflammatory response and accompanying neuronal apoptosis, will aggravate the condition. Due to the existence of the blood–spinal cord barrier (BSCB), the existing drugs for SCI treatment are difficulty to reach the injury site and thus their efficacy is limited. In this study, we designed chitosan-modified hollow manganese dioxide nanoparticles (CM) for the delivery of resveratrol to help it pass through the BSCB. Resveratrol (Res), a poorly soluble drug, was adsorbed into CM with a particle size of approximately 130 nm via the adsorption method, and the drug loading reached 21.39 ± 2.53%. In vitro dissolution experiment, the Res release of the loaded sample (CMR) showed slowly release behavior and reached about 87% at 36 h. In vitro at the cellular level and in vivo at the animal level experiments demonstrated that CMR could alleviate significantly oxidative stress by reducing level of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and increasing glutathione peroxidase (GSH) level. Additionally, immunofluorescence (iNOS, IL-1β, and Cl caspase-3) and western blot (iNOS, cox-2, IL-1β, IL-10, Cl caspase-3, bax, and bcl-2) were used to detect the expression of related factors, which verified that CMR could also reduce inflammation and neuronal apoptosis. These results indicated that CM, as a potential central nervous system drug delivery material, was suitable for SCI treatment. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Article
Introduction Fecal microbiota transplantation (FMT) is a promising therapy, but it has not been used to treat neonatal necrotizing enterocolitis (NEC) due to reports of adverse side effects. Probiotics are considered relatively safe with practicable administrative procedures; however, no systematic research has compared the results of FMT and probiotic consortium transplantation (PCT) on oxidative stress in the intestines of patients with NEC. We conducted this study to provide a basis for optimizing NEC therapy. Methods Eight-day-old newborn C57BL/6 mice were randomly divided into the following four groups: the dam-fed group (control group); the NEC induction group (NEC group); the NEC induction and transplantation of Lactobacillus reuteri and Bifidobacterium infantis consortium group (NEC + PCT group); and the NEC induction and the FMT group (NEC + FMT). Intestinal injury, oxidative stress indexes, intestinal barrier function, and inflammatory cytokines were assessed in the terminal ileum. Results FMT more effectively modulates oxidative stress in the intestine than does PCT; however, the difference between the effects of PCT and FMT was not significant. The protective effect was associated with enhanced antioxidant capacity, regulation of the main components of the mucus layer, reduced inflammatory reactions, and improved intestinal integrity. Conclusions Intestinal dysbiosis affects oxidative stress, inflammatory response, and mucosal integrity. Although FMT is more effective than PCT in regulating oxidative stress, PCT may be preferred in pediatrics because the proportion and dose of transplanted bacteria can be standardized and individualized according to individual conditions.
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Fluctuations of dissolved oxygen (DO) frequently lead to a hypoxic condition in aquaculture, and hypoxia exerts tremendously adverse effects on fish. The present study mainly investigated the effects of chronic hypoxia on growth performance, antioxidant capacity and protein turnover of largemouth bass (Micropterus salmoides). The fish were exposed to normoxic (86%–95% DO saturation), mild hypoxic (51%–60% DO saturation) and severe hypoxic (17%–26% DO saturation) conditions for 6 weeks, respectively. Results showed that chronic hypoxia significantly reduced the weight gain rate, specific growth rate and feed intake of largemouth bass. The activities of SOD and CAT in serum, as well as SOD and GPX in muscle, were significantly increased in the severely hypoxic condition. The histological analysis showed that the mean diameter of myofiber was significantly decreased during severe hypoxia. Additionally, the levels of gene and protein revealed that chronic severe hypoxia inhibited protein synthesis by downregulating the HIF-1α/REDD1/mTOR signal pathway and promoted protein degradation by activating the pathways of ubiquitin-proteasome, autophagy-lysosome and calcium proteasome. Overall, this study indicated that chronic hypoxia decreased the growth performance of largemouth bass. Meanwhile, chronic severe hypoxia not only enhanced antioxidant capacity, but also contributed to orient in the balance of protein turnover towards catabolism thus causing muscle atrophy. We suggested that for better growth of fish, the dissolved oxygen concentration should be maintained above 60% DO saturation in aquaculture.
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Malondialdehyde (MDA) is an endogenous genotoxic product of lipid peroxidation and its accumulation in the human body is associated with various diseases. To accurately understand the role of MDA in physiological and pathological processes, it is of great significance to develop a robust and reliable method for rapid detection of MDA. Hence, we proposed a surface-enhanced Raman spectroscopy (SERS) based method for MDA analysis, which employed 4-aminophenylthiophenol (PATP) as a SERS microprobe to recognize and quantify MDA. Qualitative analysis of MDA was performed using the fingerprint Raman spectrum of MDA adducts, and quantitative analysis of MDA was conducted using the characteristic peak of PATP at 1083 cm⁻¹ as the internal standard. MDA detection can be performed in a mild reaction environment and the detection limit was below 0.50 μM. The proposed method successfully detected MDA in fresh blood samples and found satisfactory recovery rates in spiked samples. The proposed method allows reliable detection of endogenous toxic compounds in blood plasma, which is of great significance for monitoring oxidative stress indicators, such as lipid peroxidation rate and intensity, potential antioxidant capacity, and the degree of tissue peroxidation damage.
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Oxidative stress plays a central role in polycystic ovary syndrome (PCOS). Catalpol (CAT) is the active ingredient of Rehmannia glutinosa Libosch which has therapeutic effect on PCOS. However, little is known about the mechanism of CAT in PCOS. PCOS rats were induced by subcutaneous injection of dehydroepiandrosteronec for four weeks and then were treated with CAT (50 mg/kg) or carboxyl methyl cellulose (the solvent of CAT) or normal saline for another 4 weeks. Histopathological observation of ovarian tissues, the levels of testosterone, estradiol and progesterone in rat plasma samples, the oxidative stress related-indexes and the expressions of NF-κB pathway-related proteins were determined. KGN cell (human ovarian granulosa cell line) was used as PCOS cell model and was transfected with siSIRT1 in the presence of CAT. The viability, proliferation and apoptosis of cells and the levels of SIRT1 and NF-κB pathway-related proteins were measured. CAT lessened the anthropometric indices and improved ovarian damage in PCOS model rats, and reduced the levels of testosterone, estradiol, progesterone and MDA, increased GSH content, and elevated the activities of catalase, GSH-Px and SOD in ovarian tissues of PCOS model rats. CAT up-regulated SIRT1 level and inhibited the activation of NF-κB signaling pathway in PCOS rat model and KGN cells. Silencing SIRT1 increased the viability and proliferation, whilst decreased the apoptosis of CAT-treated KGN cells. Silencing SIRT1 counteracted the effect of CAT on the level of oxidative stress-related factors and NF-κB signaling pathway in KGN cells. CAT attenuated PCOS by regulating SIRT1 mediated NF-κB signaling pathway.
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Giant grouper (Epinephelus lanceolatus) is an emerging aquaculture species in Southeast Asia and Australia with limited knowledge of its nutrient requirements and effects of supplements on its physiology. The present study investigated the effects of astaxanthin, vitamin E, and combinations on growth performance, body coloration, and the antioxidant status of juvenile giant grouper. Nine isonitrogenous (crude protein = 65 % ± 0.7 %) and isolipidic (crude lipid = 10 % ± 0.3 %) diets were formulated using a 3 × 3 factorial design, including three levels astaxanthin (0, 75, and 150 mg/kg) and vitamin E (0, 250, and 500 mg/kg), respectively. Each of the nine diets was fed to triplicate groups of 15 giant grouper (18.04 ± 0.92 g) for 30 days. Giant grouper fed the different diets exhibited no significant differences (p > 0.05) in specific growth rate (4.87 %/day - 5.21 %/day). However, dietary astaxanthin supplementation significantly enhanced the redness (a*), yellowness (b*b*), chroma, and hue values of the fin, regardless of the dose supplemented. Giant grouper fed astaxanthin at 75 and 150 mg/kg diet were more yellow and had three times higher b* values than fish fed non-supplemented diets. Further, total antioxidant capacity (TAC; mmol Trolox equivalent) in liver tissues was significantly increased in fish fed any of the astaxanthin-supplemented diets (p ≤ 0.05). In contrast, TAC levels were not affected by vitamin E supplementation. Malondialdehyde (MDA) levels were not significantly (p > 0.05) affected by astaxanthin or vitamin E. Findings from this study will contribute toward a better understanding of the dietary effects of antioxidant and pigment in juvenile giant grouper. We present that dietary treatment can modulate giant grouper pigmentation and may be used in the live fish trade. Further, this study contributes to narrowing the knowledge gap in formulating appropriate diets for giant grouper, which to date is fed diets formulated for other species.
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The current study was designed to explore the effect of fermented camel milk, plant sterols and their combination on the blood levels of sd-LDL and atherogenicity in rats fed on high-fat-cholesterol diets (HFC). Forty male Wistar rats were distributed into five groups: Normal control (NC), Positive control (PC, HFC), plant sterol (PS, HFC containing 1% (w/w) β-sitosterol:Stigmasterols; 9:1), FM (HFC containing 4% (w/w) lyophilized fermented camel milk), and PSFM (HFC containing 1% (w/w) plant sterols +4% (w/w) lyophilized fermented camel milk). Antioxidant activity showed that beta-sitosterol had the highest radical scavenging activity, followed by fermented camel milk and stigmasterol (p < 0.05). Feeding rats on HFC for 8 weeks resulted in a significant (p < 0.05) increase in blood lipids of PC group compared with NC group. Administration of PS, FM, and PSFM resulted in a significant reduction in atherogenic index (50, 24.5, and 41.5 %, p < 0.05), and sd-LDL levels (73, 45, and 59%, p < 0.05), respectively. Only the FM group showed a significant reduction in triglycerides levels of rats. Administration of PS, FM and PSFM decreased serum MDA levels significantly by 58.7, 45.4, and 69% (p < 0.05), and increased total antioxidant capacity by 35.9, 84.8, and 38.3% (p < 0.05), respectively. This is the first report to the best of our knowledge that shows fermented camel milk enriched with plant sterol could reduce atherogenesis and cardiovascular diseases activity via inhibition of the status of small dense LDL and oxidative stress.
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Background: This study aims to investigate the possible protective effects of rutin, also called vitamin P1, against pulmonary contusion induced by blunt chest trauma in a rat model. Methods: Thirty male albino Wistar rats were separated into three equal groups as healthy group, trauma group, and trauma+rutin group. After anesthesia provided by intraperitoneal administration of 60 mg/kg ketamine and xylazine by inhalation at appropriate intervals, 200 g weight was dropped from 1 m height to the anterior chest wall of the animals in the trauma group (n=10) and trauma+rutin group (n=10) and pulmonary contusion was created. Thirty min after the trauma, 50 mg/kg of rutin was administered into the stomach of trauma+rutin group animals orally with gavage. The rats received rutin once daily for two days and were sacrificed 48 h later. Their lung tissues were removed and examined biochemically and histopathologically. Results: Nuclear factor-kappa B, cyclooxygenase-2, and malondialdehyde levels increased in the trauma group compared to the healthy group, and rutin administration prevented this increase. Total glutathione levels decreased in the trauma group, and rutin administration also prevented this decrease. The histopathological findings were compatible with the biochemical findings. Conclusion: Our study results suggest that rutin has a protective effect on contused lung tissue in rats.
Article
This study investigated the effects of different doses of rutin on the growth performance, immunity, intestinal barrier, and antioxidant capacity of broilers. A total of two hundred and fifty-six 1-day-old male broilers were divided into 4 groups and fed basal diets supplemented with 0 (control group), 250, 500 and 1,000 mg rutin/kg, respectively, for 42 days. In the starter period (days 1–21) and whole trial period (days 1–42), broilers fed diets containing 500 mg rutin/kg had significantly (p < 0.05) higher average daily feed intake, body weight and average daily gain and better feed conversion ratio. Dietary 500 mg rutin/kg increased the villus height, villus height to crypt depth ratio and villus area, while reducing the B cell lymphoma 2 associated X mRNA expression (p < 0.05). Dietary 500 mg rutin/kg increased the level of IgA in serum and decreased serum tumour necrosis factor-α (TNF-α) content, and the nuclear factor kappa-B, interleukin-2 and TNF-α mRNA expression in jejunal mucosa (p < 0.05). Simultaneously, 500 and 1,000 mg rutin/kg significantly decreased serum diamine oxidase activity, D-lactic acid and lipopolysaccharide concentration, increased activities of total superoxide dismutase and total antioxidant capacity in jejunal mucosa (p < 0.05), and upregulated mRNA expressions of genes related to intestinal barrier and antioxidant capacity in jejunal mucosa (p < 0.05). These findings indicate that dietary rutin, especially at 500 mg/kg, improves broilers’ growth performance, intestinal barrier function, immunity, and antioxidant capability, which may be related to the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. • Highlights • Dietary rutin improved growth performance, jejunal morphology, and intestinal barrier function. • Dietary rutin enhanced the immunity via inhibiting NF-κB, and improved antioxidant capacity via activating Nrf2/HO-1 pathway in broilers. • The optimal dose of rutin was 500 mg/kg in broiler diet.
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The body color of aquatic products is a key indicator that aquaculture practitioners use to evaluate health status and consumers use to judge quality. Carotenoids are natural pigments that are mainly pigmented compounds responsible for red, yellow, and orange coloration. They have important functions, such as immune and antioxidant modulation. Recently, a novel strain of Pelodiscus sinensis with bright yellow color, named the Yongzhang golden turtle (YGT), was obtained through selective breeding. However, the actions of carotenoids on its coloration, antioxidant activities and immune competence have not been investigated yet. In this study, we examined the concentration of carotenoids in the skin and calipash of the atrovirens wild-type turtle (AWT) and YGT by spectrophotometry and found that the concentration of carotenoids in the YGT was significantly higher than that in the AWT. Then, we measured relevant antioxidant activity indicators, including total antioxidant capacity (T-AOC) and malondialdehyde (MDA), by commercial kits in the YGT and AWT, identifying higher activities of T-AOC in the YGT compared with those in the AWT, while MDA contents were decreased in the YGT compared to those in the AWT. We quantified the immune competence of the YGT and AWT using plasma bacteria-killing ability (BKA) and immunoglobulin M (IgM) expression. Compared to plasma from the AWT, that of the YGT showed higher antibacterial activity against Escherichia coli, Aeromonas hydrophila, Staphylococcus aureus, Salmonella typhimurium, and Citrobacter freundii. However, there was no difference in IgM expression between the YGT and AWT. Correlation analysis suggested that carotenoid concentration was positively associated with T-AOC and BKA, and negatively associated with MDA. In conclusion, the bright yellow color of YGT was mainly caused by carotenoids, which could enhance the antioxidant capacity and immune competence. Therefore, the YGT, with yellow coloration, possesses a high ornamental value and is much better in quality than the AWT.
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Oxidative stress is a key factor in the development of inflammatory diseases. Elimination of reactive oxygen species (ROS) in the inflamed colon has been confirmed as an effective strategy to alleviate inflammatory bowel disease (IBD). The conventional approaches will cause systemic absorption and potential side effects. To address these issues, we develop a nanomedicine ([email protected] NPs) that is capable of delivering to target inflammatory lesions by electrostatic adsorption, subsequently effectively scavenging the excess ROS and alleviating inflammation to ameliorate ulcerative colitis (UC). In the DSS induced acute colitis mice model, [email protected] NPs can significantly reduce the production of pro-inflammatory cytokines, alleviate oxidative stress, and promote the favorable recovery of the damaged colonic tissue. These results indicate that [email protected] NPs are able to effectively alleviate intestinal inflammation and provide strong theoretical support for the treatment of other inflammatory diseases.
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Small molecules that induce lipoperoxidation have been proposed repeatedly as potential antiviral drugs based on a presumed unique sensitivity of virions to this type of damage. Several small molecules that inactivate virions without affecting cells have been proposed to act primarily by inducing lipoperoxidation.
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Although, copper (Cu) is commonly used in aquaculture as a chemotherapeutic agent to prevent and control algal blooms and bacterial infections, it could negatively impact the health and performance of aquatic animals. Moreover, sodium butyrate used as a feed additive plays a potential role in improving the performance and well-being of many aquatic species. Therefore, in this study, Nile tilapia, Oreochromis niloticus (L.) with average weight of 8.5–9.5 g, were fed on diets containing nanosized sodium butyrate (NSB) at levels of 0.0 (control), 0.25, 0.5, 1.0, 2.5, 5.0, and 10 mg/kg feed for eight weeks. Following the feeding period, fish from each treatment were subsequently exposed to waterborne Cu (0.5 mg/L) for further ten days. Results obtained herein revealed that with optimum values of 1.0–2.5 mg/kg diet, dietary NSB linearly and quadratically boosted fish performance, with no effects on the whole body composition of Nile tilapia. We also observed that when dietary NSB levels in Nile tilapia diets were increased from 1.0 to 10.0 mg/kg feed, serum alpha-amylase, lipase, and total proteases activities were linearly and quadratically increased compared with the control group. In NSB-fed fish, no changes in glucose, aspartate (AST), or alanine aminotransferase (ALT) levels, but significant increases in total proteins and total lipids levels were seen (notably at 2.5–10.0 mg/kg feed). Higher values of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), lysozyme (Lys), respiratory burst activity (RBA), and total immunoglobulin (total Ig) were also observed in NSB-fed fish particularly at 2.5–10.0 mg NSB/kg feed. Contrastively, the control fish exhibited highest glucose, AST, and ALT values coupled with lower total proteins and total lipids values after Cu exposure. The control fish exposed to Cu toxicity showed higher values of SOD, CAT, and GPx, as well as malondialdehyde and nitric oxide levels coupled with lowest values of Lys, RBA, and total Ig. Also, the Cu residue in the control fish’s body post-Cu exposure was significant higher than those of fish fed on NSB diets (5.0–10 mg/kg feed). Feeding Nile tilapia on NSB significantly reduced the Cu uptake and, subsequently, the Cu residue in the fish body. Hence, significant recovery of the above-mentioned variables was observed in NSB-fed groups, especially at 2.5–10.0 mg/kg feed treatments. Therefore, this study demonstrated that dietary NSB (1.0–2.5 mg/kg feed) has significant role in boosting fish performance, enhancing antioxidant-immune biomarkers, and reducing the Cu uptake and bioaccumulation in fish bodies.
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For many cancer patients, chemotherapy produces untreatable life-long neurologic effects termed chemotherapy-related cognitive impairment (CRCI). We discovered that the chemotherapy methotrexate (MTX) adversely affects oxidative metabolism of non-cancerous choroid plexus (ChP) cells and the cerebrospinal fluid (CSF). We used a ChP-targeted adeno-associated viral (AAV) vector approach in mice to augment CSF levels of the secreted antioxidant SOD3. AAV-SOD3 gene therapy increased oxidative defense capacity of the CSF and prevented MTX-induced lipid peroxidation in the hippocampus. Furthermore, this gene therapy prevented anxiety and deficits in short-term learning and memory caused by MTX. MTX-induced oxidative damage to cultured human cortical neurons and analyses of CSF samples from MTX-treated lymphoma patients demonstrated that MTX diminishes antioxidant capacity of patient CSF. Collectively, our findings motivate the advancement of ChP- and CSF-targeted anti-oxidative prophylactic measures to relieve CRCI.
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The present study aimed to investigate the effects of dietary starch levels on growth performance, hepatic proximate composition and non‐specific immunity of juvenile snakehead (Channa argus). Seven isonitrogenous and isolipidic diets, supplemented with graded levels of α‐starch, 0%, 3.0%, 6.0%, 9.0%, 12.0%, 15.0% and 18.0%, were fed to triplicate groups of juvenile snakehead (initial body weight, 11.83 ± 0.02 g) for 8 weeks. Results showed that dietary starch levels had no significant effect on the growth performance of snakehead, while the survival rate was significantly elevated when the inclusion level of starch was higher than or equal to 9%. The content of hepatic crude protein and crude lipid was significantly reduced with the increase in dietary starch levels, while hepatic glycogen content was significantly elevated, which was partly related to the significantly increased hepatosomatic index and viscerosomatic index. The content of malondialdehyde and serum aspartate aminotransferase and aspartate aminotransferase activity was significantly elevated, while serum lysozyme activity was significantly decreased when dietary starch inclusion content exceeded 9%. Gene expression analysis revealed that the inclusion of starch exceeded 9% significantly promoting the expression of NF‐κB P65. Meanwhile, the increase in dietary starch levels led to an increased expression of pro‐inflammation factor, IL‐1β and COX‐2, and their expression in 15% and 18% starch inclusion groups was significantly higher than that in the 0% and 3% starch inclusion groups. In conclusion, the recommended dietary starch inclusion level is 9% based on the reasonable compromise of the above biomarker responses.
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Human actions are altering ecosystems worldwide. Among human‐released pollutants, ionizing radiation arises as a rare but potentially devastating threat for natural systems. The Chornobyl accident (1986) represents the largest release of radioactive material to the environment. Our aim was to examine how exposure to radiation from the Chornobyl accident influences dorsal skin coloration of Eastern tree frog (Hyla orientalis) males sampled across a wide gradient of radioactive contamination in northern Ukraine. We assessed the relationship between skin frog coloration (which can act as a protective mechanism against ionising radiation), radiation conditions, and oxidative stress levels. Skin coloration was darker in localities closest to areas with high radiation levels at the time of the accident, whereas current radiation levels seemed not to influence skin coloration in Chornobyl tree frogs. Tree frogs living within the Chornobyl Exclusion Zone had a remarkably darker dorsal skin coloration than frogs from outside the Zone. The maintenance of dark skin coloration was not linked to physiological costs in terms of frog body condition or oxidative status, and we did not detect short‐term changes in frog coloration. Dark coloration is known to protect against different sources of radiation by neutralizing free radicals and reducing DNA damage, and, particularly melanin pigmentation has been proposed as a buffering mechanism against ionizing radiation. Our results suggest that exposure to high levels of ionizing radiation, likely at the time of the accident, may have selected for darker coloration in Chornobyl tree frogs. Further studies are needed to determine the underlying mechanisms and evolutionary consequences of the patterns found here.
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This study aimed to assess the effects of dietary addition with Chlorella sorokiniana on fish growth, gut histology, antioxidant capacity, immune response, and disease resistance in rainbow trout. Three diets with similar proximate composition and different Chlorella meal levels were formulated. The control diet, 5% Chlorella diet, and 10% Chlorella diet contained 0%, 5% Chlorella meal, and 10% Chlorella meal, respectively. Each diet was assigned to triplicate tanks containing 30 fish (165.3 ± 0.6 g) in each tank. Fish were fed experimental diets for ninety days. The results showed that the addition of 5% Chlorella in the diet significantly increased feed intake by 19.3% and weight gain rate by 17.3% (P < 0.05) without affecting feed efficiency and gut histology. Diets containing Chlorella meal significantly decreased malonaldehyde contents in the plasma after the lipopolysaccharide (LPS) challenge (P < 0.05). Dietary supplementation with Chlorella meal significantly increased lysozyme (LZM) activity levels (in the head kidney) and immunoglobulin M (IgM) (in the head kidney) and complement component 3 (C3) (in the spleen) contents before the LPS challenge, and simultaneously increased LZM activity levels (in the plasma) and C3 contents (in the plasma and head kidney) after the LPS challenge (P < 0.05). Furthermore, dietary administration of Chlorella meal significantly increased the survival rate of fish infected with Aeromonas salmonicida (P < 0.05). In conclusion, C. sorokiniana can be used to improve fish growth, antioxidant capacity, and immunity.
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Both fine particulate matter (PM2.5) and ozone (O3) may have adverse effects on human health. However, previous studies on the effects of air pollutants mainly have focused on susceptible population, and evidence on healthy young adults is limited. We aimed to examine the associations of the two main air pollutants (PM2.5 and O3) with lung function, inflammation and oxidative stress in healthy young adults. We recruited 30 healthy young adults for a longitudinal panel study in Beijing and implemented health examination seven times, including lung function (FEV1 and PEF) and biomarkers of inflammation and oxidative stress (i.e. C-reactive protein, CRP; interleukin-6, IL-6; malondialdehyde, MDA) from December 2019 to May 2021. Hourly ambient air pollutants data were obtained from the closest air quality monitoring station. Linear mixed-effect model was applied to explore the associations between air pollutants and lung function, inflammation and oxidative stress. We observed higher PM2.5 exposure was associated with decrement in lung function and increment in CRP and MDA. Each 10 μg/m³ increase in PM2.5 (lag 2 day) is associated with a 17.06 ml (95% CI: −31.53, −2.58) decrease in FEV1, 46.34 ml/s (95% CI: −76.41, −16.27) decrease in PEF and increments of 2.86% (95% CI: 1.47%, 4.27%) in CRP, 1.63% (95% CI: 0.14%, 3.14%) in MDA respectively. However, there is no significant association between ozone exposure and health indicators. The study suggested that short-term exposure to PM2.5 may decrease lung function and induce inflammation and oxidative stress in healthy adults, but there is no association between O3 and each outcome.
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Pyraclostrobin (PYR), a strobilurin fungicide, has been widely used to control fungal diseases, posing potential risk to aquatic organisms. However, the toxic effects of PYR to fish remained largely unknown. In this study, common carp (Cyprinus carpio L.) was exposed to environmentally relevant levels of PYR (0, 0.5 and 5.0 μg/L) for 30 days to assess its chronic toxicity and potential toxicity mechanism. The results showed that long-term exposure to PYR induced hepatopancreas damage as evident by increased in serum transaminase activities (AST and ALT). Moreover, PYR exposure remarkably enhanced the expressions of hsp70 and hsp90, decreased the levels of antioxidant enzymes and biomarkers and promoted the reactive oxygen species (H2O2 and O2⁻) and MDA contents in carp hepatopancreas. PYR exposure also upregulated apoptosis-related genes (bax, apaf-1, caspase-3 and caspase-9) and reduced anti-apoptosis gene bcl-2 in fish hepatopancreas. Moreover, PYR exposure altered the expressions of inflammatory cytokines (IL-1β, IL-6, TNF-α and TGF-β) in the serum and hepatopancreas and the level of NF-κB p65 in the hepatopancreas. Further research indicated that PYR exposure markedly changed the levels of immune parameters (LYZ, C3, IgM, ACP and AKP) in the serum and/or hepatopancreas, indicating that chronic PYR exposure also has immunotoxicity on fish. Additionally, we found that PYR exposure upregulated p38 and jnk MAPK transcription levels, suggesting that MAPK may be play important role in PYR-induced apoptosis and inflammatory response in the hepatopancreas of common carp. In summary, PYR exposure induced oxidative stress, triggered apoptosis, inflammatory and immune response in common carp, which can help to elucidate the possible toxicity mechanism of PYR in fish.
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Climate warming is intensifying on the Tibetan Plateau and poses a serious threat to amphibians that live there. Although hibernation physiology and ecology of Nanorana parkeri, a frog species native to the Tibetan plateau, has been well studied, little information is available about the physiological and biochemical responses to acute rising temperature. Here, we conducted an acute warming experiment comparing hibernating N. parkeri (acclimated at 4 °C) and frogs acutely warmed to 10 °C for 12 hours, comparing indicators of oxidative stress and antioxidant defense between the two groups. Acute warming led to a significant increase in the content of oxidized glutathione and the ratio of oxidized:reduced glutathione in liver and muscle, indicating that rapid warming causing oxidative stress could be a negative factor for frogs inhabiting the Tibetan plateau. Malondialdehyde content increased by 57% only in muscle but decreased significantly in three tissues. Protein carbonyl groups rose by 15% in brain, 28% in liver, and 21% in muscle after heat exposure but vitamin C content in heart decreased by 44%. Acute heat exposure also induced tissue-specific upregulation of antioxidant enzyme activities. Catalase activity increased by 27% in heat-exposed frogs, as compared to controls, and glutathione peroxidase activity rose by 12% in brain, 30% in liver, and 12% in muscle. Glutathione-S-transferase activity was also enhanced in heart and muscle of heat-exposed frogs. Acute warming also resulted in a rise in total antioxidant capacity in all tissues examined except kidney, relative to controls. In summary, our findings show that acute heat exposure to hibernating N. parkeri causes a tissue-specific increase in oxidative damage and antioxidant defenses, with skeletal muscle being the most affected tissue. These results reveal the physiological responses to acute temperature change in overwintering N. parkeri.
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Lipid peroxidation often occurs in response to oxidative stress, and a great diversity of aldehydes are formed when lipid hydroperoxides break down in biological systems. Some of these aldehydes are highly reactive and may be considered as second toxic messengers which disseminate and augment initial free radical events. The aldehydes most intensively studied so far are 4-hydroxynonenal, 4-hydroxyhexenal, and malonaldehyde. The purpose of this review is to provide a comprehensive summary on the chemical properties of these aldehydes, the mechanisms of their formation and their occurrence in biological systems and methods for their determination. We will also review the reactions of 4-hydroxyalkenals and malonaldehyde with biomolecules (amino acids, proteins, nucleic acid bases), their metabolism in isolated cells and excretion in whole animals, as well as the many types of biological activities described so far, including cytotoxicity, genotoxicity, chemotactic, and effects on cell proliferation and gene expression. Structurally related compounds, such as acrolein, crotonaldehyde, and other 2-alkenals are also briefly discussed, since they have some properties in common with 4-hydroxyalkenals.
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The present research describes studies which address the mechanism of prostacyclin (PGI2) and thromboxane A2 (TXA2) biosynthesis. In addition to prostaglandin H1 (PGH1), PGG2, PGH2, and PGH3, also 8-iso-PGH2, 13(S)-hydroxy-PGH2, and 15-keto-PGH2 were applied to determine the substrate specificities and kinetics of prostacyclin and thromboxane synthase in more detail. Human platelet thromboxane synthase converted PGH1, 8-iso-PGH2, 13(S)-hydroxy-PGH2 and 15-keto-PGH2 into the corresponding heptadecanoic acid (C17) plus malondialdehyde, whereas the thromboxane derivative was formed only from PGG2, PGH2, and PGH3 together with the corresponding C17 metabolite and malondialdehyde in a 1:1:1 ratio. In contrast, PGG2, PGH2, 13(S)-hydroxy-PGH2, 15-keto-PGH2 and PGH3 were almost completely isomerized to the corresponding prostacyclin derivative by bovine aortic prostacyclin synthase, whereas PGH1 and 8-iso-PGH2 only produced the corresponding C17 hydroxy acid plus malondialdehyde. Isotope-labeling experiments with [5,6,8,9,11,12,14,15-²H]PGH2 revealed complete retention of label and no isotope effect in the course of thromboxane biosynthesis, but the loss of one ²H atom at C-6 with an isotope effect of 1.20 during PGI2 formation. Prostacyclin and thromboxane synthase bind both 9,11-epoxymethano-PGF2α and 11,9-epoxymethano-PGF2α at the heme iron, but according to their difference spectra in opposite ways with respect to the 9- and 11-position. In agreement with published model studies, a cage radical mechanism is proposed for both enzymes according to which the initial radical process is terminated through oxidation of carbon-centered radicals by the iron-sulfur catalytic site, followed by ionic rearrangement to PGI2 or TXA2. Various Fe(III) model compounds as well as liver microsomes or cytochrome P-450CAM can also form small amounts of PGI2 and TXA2, but mainly yield 12(S)-hydroxy-5,8,10-heptadecatrienoic acid plus malondialdehyde probably by a radical fragmentation pathway.
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The present research describes studies which address the mechanism of prostacyclin (PGI2) and thromboxane A2 (TXA2) biosynthesis. In addition to prostaglandin H1 (PGH1), PGG2, PGH2, and PGH3, also 8-iso-PGH2, 13(S)-hydroxy-PGH2, and 15-keto-PGH2 were applied to determine the substrate specificities and kinetics of prostacyclin and thromboxane synthase in more detail. Human platelet thromboxane synthase converted PGH1, 8-iso-PGH2, 13(S)-hydroxy-PGH2 and 15-keto-PGH2 into the corresponding heptadecanoic acid (C17) plus malondialdehyde, whereas the thromboxane derivative was formed only from PGG2, PGH2, and PGH3 together with the corresponding C17 metabolite and malondialdehyde in a 1:1:1 ratio. In contrast, PGG2, PGH2, 13(S)-hydroxy-PGH2, 15-keto-PGH2 and PGH3 were almost completely isomerized to the corresponding prostacyclin derivative by bovine aortic prostacyclin synthase, whereas PGH1 and 8-iso-PGH2 only produced the corresponding C17 hydroxy acid plus malondialdehyde. Isotope-labeling experiments with [5,6,8,9,11,12,14,15-2H]PGH2 revealed complete retention of label and no isotope effect in the course of thromboxane biosynthesis, but the loss of one 2H atom at C-6 with an isotope effect of 1.20 during PGI2 formation. Prostacyclin and thromboxane synthase bind both 9,11-epoxymethano-PGF2 alpha and 11,9-epoxymethano-PGF2 alpha at the heme iron, but according to their difference spectra in opposite ways with respect to the 9- and 11-position. In agreement with published model studies, a cage radical mechanism is proposed for both enzymes according to which the initial radical process is terminated through oxidation of carbon-centered radicals by the iron-sulfur catalytic site, followed by ionic rearrangement to PGI2 or TXA2. Various Fe(III) model compounds as well as liver microsomes or cytochrome P-450CAM can also form small amounts of PGI2 and TXA2, but mainly yield 12(S)-hydroxy-5,8,10-heptadecatrienoic acid plus malondialdehyde probably by a radical fragmentation pathway.
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A simple, reliable, and reproducible fluorometric method for measuring thiobarbituric acid-reactive substances (TBARS) in serum is proposed, based on the reaction between malondialdehyde (MDA) and thiobarbituric acid. Formation of TBARS was complete at pH 2.4-2.6, but extraction with n-butanol proved complete only at lower pH, i.e., 1.6-1.7. Analytical recoveries of MDA added to serum were 94%-101%; within- and between-run CVs were 2.4-3.6% and 4.6-5.5%; and the detection limit for TBARS in serum was 0.10 mumol/L. Optimized conditions included: (a) collection of either serum or heparinized plasma, (b) preservation from in vitro autoxidation by glutathione and EDTA, and (c) storage at -20 degrees C up to 35 days. The mean (+/- SD) TBARS concentration in 47 healthy adults was 1.01 (0.21) mumol/L; no sex-related difference was observed. Higher concentrations were measured in patients with renal insufficiency undergoing hemodialysis and in patients with insulin-dependent diabetes, chronic pancreatitis, or liver cirrhosis.
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Malondialdehyde (MDA) is one of the most frequently used indicators of lipid peroxidation. To generate reliable reference intervals for plasma malondialdehyde (P-MDA), a reference sample group was established in Funen, Denmark. The group consisted of 213 individuals (107 men, 106 women), ages 20-79 years. P-MDA was measured in EDTA-treated plasma after derivatization by thiobarbituric acid (TBA) and separation on HPLC. UV detection was performed at 532 nm. A reference interval was calculated as recommended by IFCC with REFVAL 3.42. The estimated reference limits (0.025 and 0.975 fractals) for the group were 0.36 and 1.24 mumol/L. The data were analyzed for gender- and age-related differences. Analysis of variance showed no interaction between gender and age, but separate analyses showed an independent effect of gender (P = 0.03), but not of age (P = 0.11). Daily smokers had a slightly higher average concentration of P-MDA than nonsmokers (P = 0.05), and P-MDA correlated with daily exposure to cigarette smoke (r = 0.162; P = 0.03). A positive correlation was also demonstrated between P-MDA and weekly alcohol consumption (r = 0.153; P = 0.03). Within-subject and day-to-day variations of P-MDA indicated that the potential of P-MDA as a biomarker for individuals is questionable. However, on a group basis, the present data support that P-MDA may be a potential biomarker for oxidative stress.
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Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has been detected in healthy human liver and leukocyte DNA. Analytical methods used so far for the detection of M1-dG have not been applied to a large number of individuals or variety of samples. Often, only a few microg of DNA from human tissues are available for analysis and a very sensitive assay is needed in order to detect background levels of M1-dG in very small amounts of DNA. In this paper, the development of an immunoslot blot (ISB) assay for the measurement of MI-dG in 1 microg of DNA is described. The limit of detection of the assay is 2.5 adducts per 10(8) bases. A series of human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n = 42) of M1-dG per 10(8) normal bases were detected in white blood cell and gastric biopsy DNA, respectively. Results on four human samples were compared with those obtained using an HPLC/32P-post-labelling (HPLC/PPL) method previously developed and indicated a high correlation between M1-dG levels measured by the two assays. The advantages of ISB over other assays including HPLC/PPL, such as the possibility of analysing 1 microg DNA/sample and the fact that it is less time-consuming and laborious, means that it can be more easily used for routine analysis of a large number of samples in biomonitoring studies.
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Malondialdehyde (MDA) is a major lipid peroxidation product that is mutagenic and tumorigenic. MDA-modified DNA adducts have been detected in animal and human tissues and may be a marker of human cancer risk. An immunohistochemical method, using a previously generated monoclonal antibody specific for MDA-DNA adducts, has been developed for the detection and quantification of DNA damage in human oral mucosa cells. The method was used initially on woodchuck liver cells treated with and without MDA, and then applied to the detection of adducts in oral mucosa cells of smokers and non-smokers. Levels of DNA damage were elevated in 25 smokers (mean relative staining intensity 97 +/- 41) compared with 25 age-, race- and sex-matched non-smokers (74 +/- 17, P < 0.02). These results demonstrate that MDA-DNA adducts can be measured in single cells of human samples by an immunohistochemical method. This methodology provides a simple way to monitor MDA-DNA damage and should be useful for studies investigating the role of exogenous and endogenous agents in oxidative stress and carcinogenesis.
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Malondialdehyde (MDA) is one of the most frequently used indicators of lipid peroxidation. To generate reliable reference intervals for plasma malondialdehyde (P-MDA), a reference sample group was established in Funen, Denmark. The group consisted of 213 individuals (107 men, 106 women), ages 20–79 years. P-MDA was measured in EDTA-treated plasma after derivatization by thiobarbituric acid (TBA) and separation on HPLC. UV detection was performed at 532 nm. A reference interval was calculated as recommended by IFCC with REFVAL 3.42. The estimated reference limits (0.025 and 0.975 fractals) for the group were 0.36 and 1.24 μmol/L. The data were analyzed for gender- and age-related differences. Analysis of variance showed no interaction between gender and age, but separate analyses showed an independent effect of gender (P = 0.03), but not of age (P = 0.11). Daily smokers had a slightly higher average concentration of P-MDA than nonsmokers (P = 0.05), and P-MDA correlated with daily exposure to cigarette smoke (r = 0.162; P = 0.03). A positive correlation was also demonstrated between P-MDA and weekly alcohol consumption (r = 0.153; P = 0.03). Within-subject and day-to-day variations of P-MDA indicated that the potential of P-MDA as a biomarker for individuals is questionable. However, on a group basis, the present data support that P-MDA may be a potential biomarker for oxidative stress.
Article
Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M 1 -dG), has been detected in healthy human liver and leukocyte DNA. Analytical methods used so far for the detection of M 1 -dG have not been applied to a large number of individuals or variety of samples. Often, only a few μg of DNA from human tissues are available for analysis and a very sensitive assay is needed in order to detect background levels of M 1 -dG in very small amounts of DNA. In this paper, the development of an immunoslot blot (ISB) assay for the measurement of M 1 -dG in 1 μg of DNA is described. The limit of detection of the assay is 2.5 adducts per 10 8 bases. A series of human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n = 42) of M 1 -dG per 10 8 normal bases were detected in white blood cell and gastric biopsy DNA, respectively. Results on four human samples were compared with those obtained using an HPLC/ 32 P-post-labelling (HPLC/PPL) method previously developed and indicated a high correlation between M 1 -dG levels measured by the two assays. The advantages of ISB over other assays including HPLC/PPL, such as the possibility of analysing 1 μg DNA/sample and the fact that it is less time-consuming and laborious, means that it can be more easily used for routine analysis of a large number of samples in biomonitoring studies.
Article
Malondialdehyde (MDA) is a major lipid peroxidation product that is mutagenic and tumorigenic. MDA-modified DNA adducts have been detected in animal and human tissues and may be a marker of human cancer risk. An immunohistochemical method, using a previously generated monoclonal antibody specific for MDA-DNA adducts, has been developed for the detection and quantification of DNA damage in human oral mucosa cells. The method was used initially on woodchuck liver cells treated with and without MDA, and then applied to the detection of adducts in oral mucosa cells of smokers and non-smokers. Levels of DNA damage were elevated in 25 smokers (mean relative staining intensity 97 ± 41) compared with 25 age-, race- and sex-matched non-smokers (74 ± 17, P < 0.02). These results demonstrate that MDA-DNA adducts can be measured in single cells of human samples by an immunohistochemical method. This methodology provides a simple way to monitor MDA-DNA damage and should be useful for studies investigating the role of exogenous and endogenous agents in oxidative stress and carcinogenesis.
Article
For the first time a fluorimetric-kinetic method for the determination of malonaldehyde (MLD) is proposed. The fluorescence emission of the thiobarbituric acid (TBA)-MLD reaction product has been monitored at 553 nm (excitation wavelength 515 nm), and the instrumental and experimental variables have been studied. A selective and fast kinetic-fluorimetric determination of malonaldehyde is proposed. The sensitivity of the method is very high, the detection limit is 0.30 ng ml−1, the application range is between 1.1 and 50 ng ml−1, and the determination time per sample is 500 s. The kinetic-fluorimetric method has been applied in the determination of two types of pathological human serum: rheumatic and hyperlipemic serum. In both cases, perchloric acid is used to precipitate the proteins.
An acetalation-acid decomposition procedure was developed to investigate the formation of malonaldehyde from a wide assortment of primary and secondary lipid oxidation products. The formation of malonaldehyde as the tetramethyl acetal derivative was determined quantitatively by gas chromatography with an internal standard technique and identified by gas chromatography-mass spectrometry. Five-membered hydroperoxy epidioxides and 1, 3-dihydroperoxides were found to be the most important precursors of malonaldehyde. 1, 4-Dihydroperoxides were less important, and monohydroperoxides were the least significant sources of malonaldehyde. No malonaldehyde was produced from either a six-membered hydroperoxy epidioxide or 1,7-and 1,8-dihydroperoxides. No correlation was found between the thiobarbituric acid values of the lipid oxidation products and analyses of malonaldehyde by the acetalation-acid decomposition procedure. By the specific methodology presented in this paper, the potential of lipid oxidation products to form malonaldehyde and its biological effect due to crosslinking can better be evaluated than the extensively used thiobarbituric acid test, which is not specific for most of the oxidation lipid products examined in this study.
Article
Concentrations of a peroxidation product (malondialdehyde), fluorescent chromophores, lipofuscin-like fluorescent products, superoxide dismutase, catalase, glutathione peroxidase, and vitamin E in the maternal blood and the cord blood were determined and the results obtained were related to the estimation of lipid peroxidation and protective mechanism against uncontrolled oxidative processes in late pregnancy. Serum levels of fluorescent products were higher in the maternal blood than in the cord blood, indicating less frequent lipid peroxidation in the fetus than in the mother. In support of this assumption, the three protective enzymes and vitamin E were present in relatively lower concentrations in the cord blood. Sudden exposure of the newborn infant to a normobaric atmosphere after beginning breathing seems, therefore, to cause oxidation of red blood cell membrane, denaturation of the membrane, inducing hemoglobin breakdown, and consequently hemolysis.
Article
A new colorimetric method for quantitative analysis of serum lipid peroxide, free of interference from sialic acids, has been developed. We have used the thiobarbituric acid dissolved in sodium sulfate solution and both liberation of lipid peroxide and color reaction have been performed simultaneously by heating serum protein precipitate with this reagent in a weak acid solution. The new method is specific and facilitates the precise measurements of serum lipid peroxide. The average values determined by the new method increased slightly with age in healthy subjects. In patients with sequelae of cerebrovascular disorders, serum lipid peroxide values were higher than in healthy controls. These results may demonstrate the important role of lipid peroxide in aging and cerebrovascular disorders.
Article
Autoxidation of methyl linolenate is shown to yield materials which give positive tests for both prostaglandin E and malonaldehyde, and it is suggested that both tests respond to prostaglandin-like endoperoxides which can be formed by autoxidation.
Article
The thiobarbituric acid test for malondialdehyde is widely used as an indicator of lipid peroxidation and free radical activity. We describe a simple and sensitive high performance liquid chromatographic (HPLC) method for measuring the malondialdehyde-thiobarbituric acid adduct using fluorimetric detection. Extraction into organic solvent or other complex sample preparation is not required and the assay is sensitive to less than 0.05 mumol/L. This method could easily be applied to any setting where a measure of lipid peroxidation is required.
Article
Plasma selenium (Se), zinc (Zn) and copper (Cu) levels and antioxidant metalloenzymes, glutathione peroxidase (GPX) and superoxide dismutase (SOD), were studied in 17 patients on maintenance hemodialysis (HD) (group I), 14 uremic patients (group II) and 14 healthy subjects (group III). Plasma Se levels and erythrocyte GPX were significantly lower in the HD group (for Se: 0.69 +/- 0.12 vs. 1.05 +/- 0.13 mumol/l in controls; for erythrocyte GPX: 34.4 +/- 6.4 vs. 49.2 +/- 9 IU/g hemoglobin in controls) and a significant correlation was found between the two parameters (r = 0.66, p less than 0.005). There was also a correlation between decreased plasma Zn and erythrocyte SOD activity (r = 0.58, p less than 0.02) and between decreased plasma Cu and erythrocyte SOD (r = 0.60, p less than 0.02). Plasma malondialdehyde levels were augmented in HD patients (5.08 +/- 0.26 vs. 2.55 +/- 0.15 mumol/l in controls and 2.79 +/- 0.40 mumol/l in the uremic group). The catalase activity was increased in HD patients (202 +/- 24 vs. 140 +/- 40 IU/mg hemoglobin in group III). A defective antioxidant activity may thus contribute to increased peroxidative damage to cells in the course of dialysis.
Article
Erythrocytes of diabetic patients have abnormal membrane properties. We examined in vivo membrane lipid peroxidation in erythrocytes of diabetic subjects and its possible relationship with hyperglycemia. Lipid peroxidation was assessed in fresh, untreated erythrocytes by quantitating thiobarbituric acid reactivity and an adduct of phospholipids and malonyldialdehyde (MDA), an end product of lipid peroxidation, with thin-layer chromatography of lipid extract of diabetic erythrocytes. There was a significantly increased membrane lipid peroxidation in diabetic erythrocytes compared with nondiabetic erythrocytes. The degree of membrane lipid peroxidative damage in erythrocytes was significantly correlated with the level of glycosylated hemoglobin, an index of mean glucose level for the preceding 3-4 mo. This suggests that peroxidation of membrane lipids and accumulation of MDA occurs in erythrocytes of diabetic patients.
Article
The thiobarbituric acid (TBA) reaction, quantified by colorimetry or fluorimetry, is the method most widely used for studying lipid peroxidation in both laboratory animals and in humans with disorders. However, concerns regarding its analytical specificity have often been expressed, because TBA reacts with a wide variety of chemical species to produce a pink to red color. In this study, we reacted TBA with various saturated and unsaturated aldehydes (both directly and in the presence of sucrose, fructose, and glucose), substituted pyrimidines, 2-deoxyribose, and N-acetylneuraminic acid. We also studied the TBA reaction with bilirubin, biliverdin, icteric serum, and serum containing hemolyzed erythrocytes, comparing the absorption spectra of these reaction products with that for malondialdehyde (MDA). The reaction products were also analyzed for MDA by high-performance liquid chromatography (HPLC). Although the TBA reaction with some of these compounds may not be important in biological studies, others could lead to misinterpretations of increased lipid peroxidation. Use of HPLC to quantify MDA is recommended because of its high analytical sensitivity and specificity, especially in the study of lipid peroxidation in human subjects.
Article
The definition for a sufficient vitamin E level has often been based on population studies that established the normal range of values for fasting plasma or serum vitamin E and more recently for vitamin E to total lipid ratios. These endpoints for vitamin E replacement strategies may not be readily achievable, particularly in the cholestatic patient for whom it is often impossible to reach and sustain normal levels even with massive doses of vitamin E. Vitamin E is believed to function as an antioxidant in vivo protecting membranes from lipid peroxidation. Malondialdehyde (MDA), a product of polyunsaturated fat peroxidation, was measured as the thiobarbiturate derivative in the supernatant following incubation of erythrocytes in hydrogen peroxide. The two different incubation conditions described here and the subsequent measurement of MDA appear to provide a sensitive functional assessment of vitamin E status. The clinical utility of this assay, which requires just 1.5 to 2.0 ml of whole blood, was demonstrated by comparing the percent of total MDA released from individuals regarded as vitamin E sufficient by conventional methods with vitamin E deficient subjects. The release of MDA from erythrocytes from vitamin E deficient subjects was clearly greater (44.1 +/- 18.8% vs 2.0 +/- 1.8%) than for control subjects (p less than 0.001).
Article
Apolipoprotein (apo) E-deficient transgenic mice develop marked hyperlipidemia and progressive atherosclerotic lesions. To explore whether oxidative modification of lipoproteins is involved in atherogenesis in this murine model, we performed extensive immunocytochemical studies. Atherosclerotic lesions ranging from early fatty streaks to very advanced plaques were examined from the aortic valve region and the thoracic and abdominal aorta. Using guinea pig antisera against malondialdehyde (MDA)-lysine and 4-hydroxynonenal-lysine, two epitopes generated during the oxidative modification of low-density lipoprotein (LDL), we demonstrated the presence of these "oxidation-specific epitopes" in atherosclerotic lesions. In early lesions, oxidation-specific epitopes were found predominantly in macrophage-rich areas, whereas diffuse extracellular staining predominated in necrotic areas of advanced lesions. We have previously shown that autoantibodies against MDA-lysine are present in the circulation of humans and rabbits and that the immunoglobulin fraction extracted from their lesions contains autoantibodies against several "oxidation-specific" epitopes. Sera from apoE-deficient mice also contained circulating autoantibodies to MDA-lysine, and both early and advanced lesions were rich in murine immunoglobulins. Titers of serum autoantibodies were significantly higher in apoE-deficient mice than in C57BL/6 mice. Autoantibodies in murine plasma recognized MDA-lysine epitopes in atherosclerotic lesions of rabbits, and the immunostaining was competitively inhibited by excess human MDA-LDL. Similar findings were obtained by competitive radioimmunoassay. Finally, a morphometric technique was developed and tested in these mice that allows a quantitative assessment of aortic atherosclerosis. These findings suggest that in apoE-deficient mice, lipoprotein oxidation is involved in atherogenesis and that these transgenic mice constitute an appropriate model with which to study the antiatherogenic effect of antioxidant intervention.
Article
The thiobarbituric acid (TBA) test is one of the oldest and most frequently used tests for measuring the peroxidation of fatty acids, membranes, and food products. In the food and dairy industries, the test is used as a general measure of lipid rancidity, while in medicine it remains the most commonly applied assay for lipid peroxidation to provide evidence of the involvement of free radicals in disease pathologies. The test is popular because it is simple and inexpensive. The sample under test is heated with TBA at low pH, and a pink chromogen is measured for absorbance at, or close to, 532 nm, or its fluorescence at 553 nm. The TBA test is often said to measure malondialdehyde (MDA) formed in peroxidizing lipid systems. Calibration of the test is achieved using MDA prepared in the laboratory by hydrolysis of 1,1,3,3-tetramethoxypropane or 1,1,3,3-tetraethoxypropane, and so results are frequently expressed as micromolar MDA equivalents. The availability of the technique of high-performance liquid chromatography (HPLC) is instrumental in the reevaluation of the TBA test. Many of the HPLC-based assays for the TBA test available at present have made a considerable contribution to the understanding of what the TBA test actually measures.
Article
The question of "increased lipid peroxidation" in plasma from hyperlipidaemic patients was investigated using an improved HPLC-based assay for thiobarbituric acid-reactive material. Levels of TBARS in healthy human controls were at or close to zero, provided that butylated hydroxytoluene was added to the sample with the TBA reagents. Levels of plasma TBARS in hyperlipidaemic patients were elevated, although the absolute levels were much lower than those reported previously in the literature. © 1993 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
Article
A method is described for the assay of the major malondialdehyde-deoxyguanosine adduct (M1G) based on immunoaffinity purification and gas chromatography/electron capture/negative chemical ionization/mass spectrometry. A stable isotope of M1G-deoxyribose ([2H2]M1G-dR) was used as an internal standard. Recovery of internal standard throughout the entire assay procedure was approximately 40%. The assay showed a linear response over a range of 10-1000 pg of M1G-dR and was verified by analysis of a synthetic. M1G-containing oligomer. The limit of detection in biological samples was 100 fmol/sample, corresponding to 3 adducts/10(8) bases for 1 mg of DNA. DNA was isolated from the blood of 10 healthy human donors, and M1G levels were measured. A mean value of 6.2 +/- 1.2 adducts/10(8) bases was obtained, with no obvious differences bases on age or cigarette smoking. A small, but statistically significant difference was observed between the levels in females (5.1 +/- 0.4 adducts/10(8) bases) and males 6.7 +/- 1.1 adducts/10(8) bases). The presence of M1G in leukocyte DNA was further verified by analysis using liquid chromatography/electrospray ionization mass spectrometry.
Article
Malondialdehyde (MDA) has been widely used as an index of lipoperoxidation in biological and medical sciences as well as in the food industry. A solid-phase extraction (SPE) of the condensation product of the MDA with 2-thiobarbituric acid (TBA) was developed using LiChrolut C18ec, 200 mg (Merck, Darmstadt, Germany), as a SPE cartridge and methanol as an eluent for sample pretreatment before HPLC analysis. The samples of blood plasma, platelet concentrates, or erythrocyte membranes (ghosts) were deproteinized by acetonitrile in the presence of sodium hydroxide prior to the reaction with TBA. The reaction mixture was processed using SPE. The SPE extracts (800 microL of methanol) were put to dryness and after dissolution with 100 microliters of mobile phase, 50 microliters was analyzed by RP-HPLC with fluorescence detection (excitation at 514 nm, emission at 556 nm). The mean MDA concentration in plasmas of 32 healthy donors was 0.37 +/- 0.25 mumol/L and the mean MDA concentration in normal ghosts was 8.3 +/- 4.1 pmol/microgram of protein content. In the case of a patient with a severe form of beta-thalassemia, the concentration of plasma MDA was raised to 1.22 mumol/L and the amount of MDA in erythrocytal ghosts was raised to 21.05 pmol/microgram of protein content. MDA concentration in platelet concentrates (six bags) in the first day of storage was 0.46 +/- 0.18 mumol/L and in the fifth day of storage was 0.55 +/- 0.44 mumol/L.
Article
Malondialdehyde (MDA) is a major lipid peroxidation product that is mutagenic and tumorigenic. The MDA-modified DNA adduct, 3-(2-deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1, 2-alpha]purin-10(3H)-one (M1G), has been detected in human tissues and may be a marker of human cancer risk. In this paper, we describe an improved 32P-postlabeling/HPLC method for sensitive detection and quantitation of this MDA-modified 2'-deoxyribonucleotide adduct. Specific improvements include (i) unequivocal structural identification of the postlabeling products, both the 3', 5'-bisphosphate of M1G (MDA-3',5'-dGDP) and the 5'-monophosphate of M1G (MDA-5'-dGMP); (ii) efficient separation of the 32P-postlabeling products by HPLC; and (iii) the incorporation of a synthetically prepared MDA-modified DNA (or the 3'-monophosphate of M1G) with a known modification level as an internal standard. This improved quantitative methodology provides high intra- and inter-assay reproducibility and has been applied to the analysis of this adduct in rodent and human samples.
Article
An important emerging issue in chemical carcinogenesis is the role that products of endogenous metabolism play in formation of covalently modified DNA. One example is the formation of alpha, beta-unsaturated aldehydes as a result of endogenous and drug-stimulated lipid peroxidation. Malondialdehyde (MDA), crotonaldehyde (CR), 2-hexenal (HX), and 4-hydroxy-2-nonenal (HNE) react covalently with 2'-deoxyguanosine (dG) and 2'-deoxyadenosine (dA) residues on DNA to form promutagenic cyclic adducts that may be important in the etiology of cancer in humans and animals. The accurate quantification of such adducts provides a powerful tool in molecular epidemiology for assessing carcinogenic risks from various lifestyle choices (e.g. diet, drug use) in humans. 32P-Postlabeling is recognized as one of the most sensitive methods available for detection of DNA adducts in human tissues, but without adequate validation such methodology can yield inaccurate quantitative measurements. We have used LC separations in conjunction with electrospray ionization MS and tandem MS (triple quadrupole and hybrid quadrupole-orthogonal acceleration time of flight analyzers) to characterize MDA-, CR-, HX- and HNE-modified dG and nucleotide (3'- and 5'-monophosphate; 3',5'-bisphosphate) adducts. These data have been used to validate 32P-postlabeling methods for quantification of low level MDA-dG adducts formed in DNA of human and animal tissues. Availability of reliable methods for quantification of endogenous DNA damage in humans and animals is essential for determining unknown etiologies of cancer and for the assessment of cancer risks in humans.
Article
A method to determine free and total (free and bound) malondialdehyde (MDA) in fresh human plasma, or in rat liver microsomes, using selected ion monitoring (SIM) gas chromatography-mass spectrometry in the electron impact mode was set up. The dideuterated internal standard, 3-hydroxy[1, 3-2H2]-2-propenal (dMDA), was added to the biological samples before their analytical manipulation. To detect free MDA the samples were reacted under mild conditions (25 degreesC, pH 4.0, 30 min) with phenylhydrazine (PH), affording 1-phenyl-1H-pyrazole and its 3, 5-dideuterated isotopomer. For the evaluation of total MDA level the plasma or microsomes were subjected, before the derivatization step, to hydrolysis in the presence of 1 M NaOH under preestablished conditions. This method offers several advantages such specificity, precision (within-day CV 2.0%, between-day CV 2.1%), linearity (0. 01-15 microM) and high sensitivity (5 pmol injected). The recovery of known added MDA amounts from plasma and microsomes, hydrolyzed or not, accounted for 98 +/- 0.6%. The free MDA levels found in the plasma and microsomes were 0.14 +/- 0.03 microM and 0.048 +/- 0.006 nmol/mg protein, respectively. The total MDA levels were 1.3 +/- 0. 07 microM in plasma and 0.36 +/- 0.04 nmol/mg protein in the microsomes.
Article
The free radical theory of aging suggests the oxygen-derived species as the causative agents and free radical scavengers as the defense systems in aging process. The exact role of the free radical scavenging effects of melatonin in aging remains to be clarified. In this experimental study, we investigated the age-related changes of malondialdehyde (MDA), a lipid peroxidation product, and glutathione (GSH) and the effects of exogenous melatonin. Plasma, liver, and lung MDA and GSH levels of 9- and 28-month-old rats were measured. Plasma, lung, and liver MDA levels of old rats were significantly higher than those of the young ones (p = 0.024, p = 0.005, and p = 0.0007, respectively). However, while the lung GSH levels were found to be significantly decreased in the control group of old rats as compared with young ones (p = 0.005), the liver GSH levels were unchanged. Plasma MDA levels were found to be significantly lower in the melatonin group of old rats as compared with the control group (p = 0.020) but lung and liver MDA levels were not significantly different. There were no significant differences in the levels of measured parameters between both groups of young rats. Our results suggest that increased levels of lipid peroxidation products may have a role in aging, and exogenous melatonin may delay the aging process of tissues by means of its free radical scavenging effects.
Article
In an attempt to identify endogenous chemicals producing DNA-protein crosslinks, we have studied in vitro crosslinking potential of malondialdehyde, a bifunctional chemical that is ubiquitously formed as a product of lipid peroxidation of polyunsaturated fatty acids. We have found that malondialdehyde readily forms crosslinks between DNA and histones under physiological ionic and pH conditions. Formation of DNA-protein crosslinks was limited to proteins that were able to bind to DNA. Malondialdehyde failed to form DNA-protein crosslinks when histone binding to DNA was prevented by elevated ionic strength or when bovine serum albumin was used in the reaction mixture. Malondialdehyde-produced DNA-histone crosslinks were relatively stable at 37 degrees C with t1/2=13.4 days. Crosslinking of histones to DNA proceeds through the initial formation of protein adduct followed by reaction with DNA. Modification of DNA by malondialdehyde does not lead to a subsequent crosslinking of proteins. Significant formation of DNA-protein crosslinks was also registered in isolated kidney and liver nuclei treated with malondialdehyde. Based on its reactivity and stability of the resulting crosslinks, it is suggested that malondialdehyde could be one of the significant sources of endogenous DNA-protein crosslinks.
Article
Malondialdehyde is a naturally occurring product of lipid peroxidation and prostaglandin biosynthesis that is mutagenic and carcinogenic. It reacts with DNA to form adducts to deoxygua