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Abstract

Oxidative stress is characterized by imbalanced reactive oxygen species (ROS) production and antioxidant defenses. Two main antioxidant systems exist. The nonenzymatic system relies on molecules to directly quench ROS and the enzymatic system is composed of specific enzymes that detoxify ROS. Among the latter, the superoxide dismutase (SOD) family is important in oxidative stress modulation. Of these, manganese-dependent SOD (MnSOD) plays a major role due to its mitochondrial location, i.e., the main site of superoxide ( [Formula: see text] ) production. As such, extensive research has focused on its capacity to modulate oxidative stress. Early data demonstrated the relevance of MnSOD as an [Formula: see text] scavenger. More recent research has, however, identified a prominent role for MnSOD in carcinogenesis. In addition, SOD downregulation appears associated with health risk in heart and brain. A single nucleotide polymorphism which alters the mitochondria signaling sequence for the cytosolic MnSOD form has been identified. Transport into the mitochondria was differentially affected by allelic presence and a new chapter in MnSOD research thus begun. As a result, an ever-increasing number of diseases appear associated with this allelic variation including metabolic and cardiovascular disease. Although diet and exercise upregulate MnSOD, the relationship between environmental and genetic factors remains unclear. © 2015 Elsevier Inc. All rights reserved.

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... The emergence of diseases of internal organs causes the tension of the antioxidant defence system, which cannot be permanent, and its «overload» contributes to the formation of an unfavourable pathological link -endotoxicosis syndrome. That is, the «oxidative stress» arises, which causes the accumulation and oxidative damage of important biological macromolecules, such as DNA, fats and proteins, which leads to cell dysfunction, and further provokes aging [3,4,5]. ...
... Antioxidant defence system has both enzymatic and non-enzymatic components, which are active during two phases of its operation. And if the first phase of the system is nonspecific (systemic), then the second phase of detoxification of xenobiotics (local level) occurs in the presence of the glutathione system enzymes and indicators of systemic and intracellular oxidative stress, in particular, manganese superoxide dismutase (MnSOD) [1,3,4,5,6]. ...
... Increasing the content of the indicated enzyme through the activation of Klotho protein synthesis has been shown to contribute to the control of the AOS system local level, that is, the process of apoptosis. Thus, raising MnSOD increases the resistance to oxidative stress, ie, «controls» the life span of the cell [4,5,6]. ...
Article
Objective: The aim: To determine the state of total antioxidant activity and the content of the mitochondrial enzyme - manganese superoxide dismutase in students with gastroesophageal reflux disease (GERD) and autoimmune thyroiditis (AIT) comorbidity. Patients and methods: Materials and methods: 120 patients with GERD and AIT, 45 patients with GERD and 42 patients with AIT were examined. The patients involved in the study were students. The international standardized GerdQ questionnaire was used. Total antioxidant activity and manganese superoxide dismutase levels were determined. Results: Results: The study showed that comorbidity of GERD and AIT was accompanied with a significant increase in the frequency and intensity of heartburn, sleep disorders and the use of additional medications to relieve symptoms. Patients with GERD and AIT had significantly lower total antioxidant activity than patients with isolated GERD and isolated AIT. At the same time, the manganese superoxide dismutase level was significantly higher in group with comorbidity than in patients with isolated diseases. Conclusion: Conclusions: The presence of concomitant AIT in patients with GERD among the student population contributes to some deviations in the clinical characteristics, inhibition of total antioxidant activity and activation of manganese superoxide dismutase.
... The SOD2 gene, located on chromosome 6q5, encodes functional SOD2 enzyme (also referred to as manganese superoxide dismutase, MnSOD) that mainly functions in the mitochondria (Bresciani, 2015). The rs4880 SNP, a substitution of A to G, results in the switch of valine (Val) to an alanine (Ala) at position 16 (Bag and Bag, 2008). ...
... The SOD2 rs4880 SNP is associated with substitution of Val at position 16 to Ala, leading to a conformational change in the secondary structure of SOD2, as the Val allele variant encodes a beta-sheet structure and the Ala allele variant encodes an alpha-helix structure (Shimoda-Matsubayashi, 1996). The switch from a beta-sheet to alpha-helix increases the mobility of this enzyme to move across the mitochondria inner membrane into the matrix, while majority of the Val allele variant encoded SOD2 were imbedded in the inner membrane (Holley, 2012;Bresciani, 2015). Furthermore, the Ala allele encoded SOD2 also has a much higher level of enzymatic activity compared with the Val allele encoded SOD2 (McAtee and Yager, 2010;Bresciani, 2015). ...
... The switch from a beta-sheet to alpha-helix increases the mobility of this enzyme to move across the mitochondria inner membrane into the matrix, while majority of the Val allele variant encoded SOD2 were imbedded in the inner membrane (Holley, 2012;Bresciani, 2015). Furthermore, the Ala allele encoded SOD2 also has a much higher level of enzymatic activity compared with the Val allele encoded SOD2 (McAtee and Yager, 2010;Bresciani, 2015). Elevated SOD2 level and its enzymatic activity of Ala variant encoded SOD2 in the mitochondria generates increased ROS as a result of SOD2-mediated H 2 O 2 generation (Shimoda-Matsubayashi, 1997;Bag and Bag, 2008;McAtee and Yager, 2010). ...
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Background: Oxidative stress is implicated in the neuropathology of bipolar disorder (BD). We investigated the association of single-nucleotide polymorphisms (SNPs) in the antioxidative genes superoxide dismutase 2 (SOD2) and glutathione peroxidase 3 (GPX3) with structural neuroimaging phenotypes in youth BD. Methods: SOD2 rs4880 and GPX3 rs3792797 SNP genotypes, along with structural magnetic resonance imaging, were obtained from 147 youth (BD=75; healthy controls (HC)=72). Images were processed using FreeSurfer, yielding surface area, volume, and thickness values for regions of interest (ROI; prefrontal cortex (PFC), caudal anterior cingulate cortex (cACC), hippocampus) and for vertex-wise whole brain analysis. Analyses controlled for age, sex, race, and intracranial volume for volume area, and thickness analyses. Result: ROI analyses revealed diagnosis-by-SOD2 rs4880 interaction effects for cACC volume and surface area, and PFC volume; in each case, there was lower volume/area in the BD GG genotype group vs. the HC GG genotype group. There was a significant BD diagnosis x GPX3 rs3793797 interaction effect for PFC surface area, where area was lower in the BD A-allele carrier group vs. the other genotype groups. Vertex-wise analyses revealed significant interaction effects in frontal, temporal, and parietal regions, related to smaller brain structure in the BD SOD2 rs4880 GG group and BD GPX3 rs3793797 A-allele carrier group. Conclusion: We found preliminary evidence that SOD2 rs4880 and GPX3 rs3792797 are differentially associated with brain structure in youth with BD, in regions that are relevant to BD. Further studies incorporating additional neuroimaging phenotypes and blood levels of oxidative stress markers are warranted.
... Another important stage of our research was the assessment of the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). They are the main antioxidant enzymes in cells [35]. The first line of antioxidant defense is the dismutation of a superoxide anion radical to oxygen and hydrogen peroxide catalyzed by SOD [33]. ...
... There are three isoforms of superoxide dismutases in human cells: cytoplasmic SOD1, mitochondrial SOD2, and extracellular SOD3; however, each catalyzes the same reaction. GPx, using glutathione, reduces hydrogen peroxide and hydroperoxides in water and alcohol [35]. Thus, GPx eliminates hydrogen peroxide and lipid peroxides. ...
... It is also found mainly in cytosol, mitochondria, and in nuclei. CAT is a peroxisomal enzyme that converts hydrogen peroxide to water and oxygen [35]. One of the primary sources of ROS in cells is the mitochondrial respiratory chain. ...
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Betulin and its derivatives, 28-propyne derivative EB5 and 29-diethyl phosphonate analog ECH147, are promising compounds in anti-tumor activity studies. However, their effect on kidney cells has not yet been studied. The study aimed to determine whether betulin and its derivatives—EB5 and ECH147—influence the viability and oxidative status of human renal proximal tubule epithelial cells (RPTECs). The total antioxidant capacity of cells (TEAC), lipid peroxidation product malondialdehyde (MDA) level, and activity of antioxidant enzymes (SOD, CAT, and GPX) were evaluated. Additionally, the mRNA level of genes encoding antioxidant enzymes was assessed. Cisplatin and 5-fluorouracil were used as reference substances. Betulin and its derivatives affected the viability and antioxidant systems of RPTECs. Betulin strongly reduced TEAC in a concentration-dependent manner. All tested compounds caused an increase in MDA levels. The activity of SOD, CAT, and GPX, and the mRNA profiles of genes encoding antioxidant enzymes depended on the tested compound and its concentration. Betulin showed an cisplatin-like effect, indicating its nephrotoxic potential. Betulin derivatives EB5 and ECH147 showed different impacts on the antioxidant system, which gives hope that these compounds will not cause severe consequences for the kidneys in vivo.
... One of the most important antioxidant enzymes is the SOD manganesedependent (MnSOD) which acts just into mitochondria. This enzyme catalyses [2] the dismutation of O 2 À to hydrogen peroxide (H 2 O 2 ), which is subsequently reduced to water, mainly by glutathione peroxidase (GPx) and also by thioredoxin reductase (TrxR) [3,4] The excess of H 2 O 2 that diffuses through mitochondria membranes to cytosol can be removed by catalase enzyme [5]. MnSOD is encoded by a nuclear gene (MnSOD gene). ...
... Different letters express significant difference between groups. compared to AV and Val-MnSOD genotypes [2]. In general, results corroborated this hypothesis tested from an experimental study with different MnSOD genotypes volunteers, using PBMC samples. ...
Article
Superoxide-hydrogen peroxide (S-HP) imbalance genetically caused by a gene polymorphism in the human manganese superoxide dismutase enzyme (Val16Ala-MnSOD) is associated with several dysfunctions and diseases. Into mitochondria, MnSOD catalyses superoxide radical producing hydrogen peroxide and oxygen. Ala-MnSOD genotype presents a high MnSOD efficiency and generates the highest H2O2 concentrations that has been associated with the risk of several cancer types. Cellular selenoenzymes glutathione peroxidase and thioredoxin reductase (TrxR) as well as catalase (CAT) are essential to H2O2 removal produced in excess in cells. Synthesis and activities of selenoenzymes are selenium dependent. The hypothesis is that AA-MnSOD cells could have an improvement on antioxidant status undergoing Seleno-l-methionine (SeMet) treatment. This study evaluated in vitro the response of peripheral blood mononuclear cells (PBMC) carriers of different Val16Ala-MnSOD genotypes exposed in parallel to 1 nM SeMet for 24 h. Cell viability, apoptosis and oxidative variables were determined using spectrophotometric, flow cytometry, fluorimetric and immunoassays protocols. Antioxidant enzymes genes modulation was performed by molecular methods. The results showed that selenoenzyme activities increased in imbalanced AA-MnSOD and VV-MnSOD cells treated with SeMet. Whereas similar response related to apoptosis and DNA damage was found in all Val16Ala-MnSOD genotypes. The results suggest a pharmacogenetic response among PBMC Val16Ala-MnSOD genotypes under SeMet treatment. These results support the idea that future in vivo studies are essential to understand the potential clinical impact of superoxide-hydrogen peroxide imbalance after use of foods or supplements containing SeMet.
... Coffee is not usually presented as a source of minerals, but due to the fact that it is consumed frequently, it can also supplement some minerals. It has been shown [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58]. ...
... Manganese is a microelement that participates in the transformation of amino acids, carbohydrates, and lipids [75,89]. It is also the main component and activator of the following enzymes: pyruvate carboxylase, glycosyltransferase, glutamine synthetase, alkaline phosphatase, and mitochondrial superoxide dismutase [56,57]. However, overexposure to manganese can be toxic. ...
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Coffee is a beverage that is very popular all over the world. Its pro-health effect has been demonstrated in many publications. This drink can counteract the effects of oxidative stress thanks to its antioxidant properties. The aim of this study was to collect data on the content of microelements with antioxidant activity (manganese, zinc, copper, iron) in coffee infusions, taking into account various factors. The study considered publications from the years 2000–2020 found in Google Scholar and PubMed databases. It was noted that coffee can provide up to 13.7% of manganese requirements per serving, up to 4.0% and 3.1% of zinc requirements for women and men, up to 2.7% and 2.1% of copper requirements for women and men, and up to 0.4% and 0.6% of iron requirements for women and men. Coffee infusions can also be a source of fluoride (up to 2.5%), chromium (up to 0.4% of daily intake for women and 0.2% for men), and cobalt (up to 0.1%). There are no data in the literature regarding the content of selenium in coffee infusions. The origin of coffee beans and the type of water used (especially regarding fluoride) may have an impact on the content of minerals in infusions. The brewing method does not seem to play an important role. As it is a very popular beverage, coffee can additionally enrich the diet with such micronutrients as manganese, zinc, and copper. This seems beneficial due to their antioxidant properties, however the bioavailability of these elements of coffee should be taken into account. It seems necessary to carry out more research in this area.
... The electron flow through the multiple redox-sensitive proteins of the complex I is accompanied by the generation of superoxide radical anions and hydrogen dioxide radicals, promoting oxidative stress ( Figure 5) [10,68,69]. Under physiological conditions, superoxide free radicals are neutralized by mitochondrial matrix-resident Mn-dependent superoxide dismutase (MnSOD), which catalyzes their conversion to hydrogen peroxide and molecular oxygen, the former thus degraded by catalases [10,[70][71][72]. Despite their high efficiency, peculiar Creatine kinase U-type (Mia-CK, Figure 4b) is found in the cristae and intermembrane space of mitochondria, being mainly expressed in the brain. ...
... The electron flow through the multiple redox-sensitive proteins of the complex I is accompanied by the generation of superoxide radical anions and hydrogen dioxide radicals, promoting oxidative stress ( Figure 5) [10,68,69]. Under physiological conditions, superoxide free radicals are neutralized by mitochondrial matrix-resident Mn-dependent superoxide dismutase (MnSOD), which catalyzes their conversion to hydrogen peroxide and molecular oxygen, the former thus degraded by catalases [10,[70][71][72]. Despite their high efficiency, peculiar macromolecu-Life 2021, 11, 386 9 of 24 lar packing of catalases in mitochondria decreases the catalytic activity of these enzymes, leading to the accumulation of hydrogen peroxide [10,71,72]. ...
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Alzheimer’s disease (AD) is a neurodegenerative disorder, affecting millions of people worldwide, a number expected to exponentially increase in the future since no effective treatments are available so far. AD is characterized by severe cognitive dysfunctions associated with neuronal loss and connection disruption, mainly occurring in specific brain areas such as the hippocampus, cerebral cortex, and amygdala, compromising memory, language, reasoning, and social behavior. Proteomics and redox proteomics are powerful techniques used to identify altered proteins and pathways in AD, providing relevant insights on cellular pathways altered in the disease and defining novel targets exploitable for drug development. Here, we review the main results achieved by both -omics techniques, focusing on the changes occurring in AD mitochondria under oxidative stress and upon copper exposure. Relevant information arises by the comparative analysis of these results, evidencing alterations of common mitochondrial proteins, metabolic cycles, and cascades. Our analysis leads to three shared mitochondrial proteins, playing key roles in metabolism, ATP generation, oxidative stress, and apoptosis. Their potential as targets for development of innovative AD treatments is thus suggested. Despite the relevant efforts, no effective drugs against AD have been reported so far; nonetheless, various compounds targeting mitochondria have been proposed and investigated, reporting promising results.
... Excessive ROS production has gained support as the primary cause in which DOX induces cardiotoxicity [78], and one of the scavengers of mitochondrial ROS is SOD2 [79]. Chaiswing et al. demonstrated that SOD2 overexpression in mice protected against DOXinduced cardiotoxicity [80]. ...
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Following myocardial infarction, reperfusion injury (RI) is commonly observed due to the excessive formation of, e.g., reactive oxygen species (ROS). Doxorubicin (DOX), a widely used anti-cancer drug, is also known to cause cardiotoxicity due to excessive ROS production. Exercise training has been shown to protect the heart against both RI- and DOX-induced cardiotoxicity, but the exact mechanism is still unknown. Neuron-derived orphan receptor 1 (NOR-1) is an important exercise-responsive protein in the skeletal muscle which has also been reported to facilitate cellular survival during hypoxia. Therefore, we hypothesized that NOR-1 could protect cardiomyocytes (CMs) against cellular stress induced by DOX. We also hypothesized that NOR-1 is involved in preparing the CMs against a stress situation during nonstimulated conditions by increasing cell viability. To determine the protective effect of NOR-1 in CMs stressed with DOX challenge, we overexpressed NOR-1 in AC16 human CMs treated with 5 µM DOX for 12 h or the respective vehicle control, followed by performing Lactate dehydrogenase (LDH) activity, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and caspase-3 activity assays to measure cell death, cell viability, and apoptosis, respectively. In addition, Western blotting analysis was performed to determine the expression of key proteins involved in cardioprotection. We demonstrated that NOR-1 overexpression decreased cell death (p < 0.105) and apoptosis (p < 0.01) while increasing cell viability (p < 0.05) in DOX-treated CMs. We also observed that NOR-1 overexpression increased phosphorylation of extracellular signal-regulated kinase (ERK) (p < 0.01) and protein expression levels of B cell lymphoma extra-large (Bcl-xL) (p < 0.01). We did not detect any significant changes in phosphorylation of protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β) and signal transducer and activator of transcription 3 (STAT3) or expression levels of superoxide dismutase 2 (SOD2) and cyclin D1. Furthermore, we demonstrated that NOR-1 overexpression increased the cell viability (p < 0.0001) of CMs during nonstimulated conditions without affecting cell death or apoptosis. Our findings indicate that NOR-1 could serve as a potential cardioprotective protein in response to Doxorubicin-induced cellular stress.
... Therefore, a better control in the production of ROS in the microenvironment of the lesion could favor the disease resolution [45]. The SOD2 with its antioxidant action, reduces enzymatically the anion superoxide accumulation by its conversion into peroxide, a less reactive ROS that will be eliminated by the action of subsequent antioxidants [15,16,46]. Thus, avoiding programmed cell death or the appearance of necrosis, favoring the malignant phenotype [47]. ...
Article
Some of the more than 200 known HPV types are essential for cervical cancer development, the third type of cancer most incident in the female population. However, for the malignant transformation occur, some cofactors are needed, as the reactive oxygen species (ROS), which can be neutralized by the antioxidant system. The SOD2 enzyme, encoded by the same name gene, is found in mitochondria and is part of the first line of defense against oxidative stress damage. Genetic polymorphisms can act by altering the efficiency of the enzyme, among which the most studied is the rs4880. Thus, the purpose of the present study was to evaluate the association of this polymorphism with HPV infection and the development of low and high grade squamous intraepithelial lesions (LSIL and HSIL) and cervical cancer, in 407 women attended by the public health system in Brazil. HPV detection in cervical secretion samples was carried out by polymerase chain reaction (PCR) and blood samples were used for polymorphism genotyping through PCR followed by restriction fragment length polymorphism (RFLP). PCR and restriction products were subjected to 10% polyacrylamide gel electrophoresis. HPV negative group (control) included 158 women and the HPV positive group (case) 249 women. The infected group was divided into No Lesion (n=90), LSIL (n=20), HSIL (n=67) and cervical cancer (n=72). The data found on socio-epidemiological characteristics and habits corroborated with data found in the literature. The distribution of genotypes in the control group was 51.9% women TC, 29.8% TT and 18.3% CC. In the case group, the distribution was 55.0% women TC, 26.1% TT and 18.9% CC. This is the first study evaluating the influence of SOD2 rs4880 polymorphism on HPV infection, the development of cervical intraepithelial lesions and cervical cancer in a Brazilian population, although additional studies are needed to corroborate the results.
... Oxidative stress is characterized by imbalanced generation of reactive oxygen species (ROS) and activity of antioxidant defenses (Bresciani et al., 2015;Arefin et al., 2020) and is known to be ...
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Methamphetamine (METH) is a major psychostimulant drug of abuse worldwide, and its neurotoxicity has been studied extensively. In addition to neurotoxicity, METH can also induce hepatotoxicity. The underlying mechanism of intestinal microorganisms in METH-induced hepatotoxicity remains unclear. In this study, mice have received antibiotics intragastrically or PBS once each day for 1 week, followed by METH or saline. The antibiotics attenuated METH-induced hepatotoxicity as evidenced by histopathological observation and biochemical analysis; furthermore, they alleviated METH-induced oxidative stress. The effect of antibiotics on METH-induced hepatotoxicity was investigated using RNA-sequencing (RNA-seq). The RNA-seq results demonstrated that antibiotics could regulate 580 differentially expressed genes (DEGs), of which 319 were upregulated after METH treatment and then downregulated with antibiotic pretreatment and 237 were first downregulated after METH administration and then upregulated after antibiotic pretreatment, in addition to 11 upregulated and 13 downregulated ones simultaneously in METH and antibiotic-pretreated groups. RNA-seq analyses revealed that TLR4 is one of the hub genes. Western blot analysis indicated that antibiotics inhibited the increase of TLR4, MyD88 and Traf6 induced by METH. This research suggests that antibiotics may play an important role in preventing METH-induced liver injury by regulating oxidative stress and TLR4/MyD88/Traf6 axis, though further investigation is required.
... SOD is an important antioxidant enzyme in the mitochondria and serves as a defense against oxidative stress (25). SOD activity was measured using a SOD assay kit (Fig. 4D). ...
Article
Shikonin, a natural naphthoquinone extracted from the roots of Lithospermumery throrhizon, possesses multiple pharmacological properties, including antioxidant, anti-inflammatory and antitumor effects. It has been hypothesized that the properties of shikonin are associated with its oxygen free radical scavenging abilities. However, the mechanism underlying the antioxidant activity of shikonin is not completely understood. The aim of the present study was to investigate the effect of shikonin against H2O2-induced oxidative injury in HT29 cells and to explore the underlying molecular mechanism. The concentration and duration of H2O2 treatment to cause maximal damage, and the effects of shikonin (2.5, 5 or 10 µg/ml) on the activity of H2O2-induced HT29 cells were determined by MTT assay. The apoptotic rate in HT29 cells was determined by annexin V/propidium iodide staining. HT29 cell cycle alteration was also analyzed by propidium iodide staining. Reactive oxygen species (ROS) production was assessed by monitoring 2',7'-dichlorofluorescin in diacetate fluorescence. Mitochondrial membrane potentials were determined by JC-1 staining. The activities of malondialdehyde, superoxide dismutase, caspase-9 and caspase-3 were measured using spectrophotometric assays. The expression levels of Bcl-2, Bax and cytochrome c were determined by western blotting. The results suggested that shikonin increased cell viability, reduced cell apoptosis and increased the proliferation index in H2O2-treated HT29 cells. Shikonin also significantly inhibited increases in intracellular reactive oxygen species (ROS), restored the mitochondrial membrane potential, prevented the release of lactic dehydrogenase and decreased the levels of superoxide dismutase and malondialdehyde in H2O2-induced HT29 cells. Furthermore, shikonin significantly decreased caspase-9 and caspase-3 activities, increased Bcl-2 expression and decreased Bax and cytochrome c expression levels in H2O2-induced HT29 cells. The results indicated that shikonin protected against H2O2-induced oxidative injury by removing ROS, ameliorating mitochondrial dysfunction, attenuating DNA oxidative damage and inhibiting mitochondrial pathway-mediated apoptosis.
... Malondialdehyde (MDA) was used as an important indicator to determinant the degree of lipid peroxidation and the level of free radicals in the body (Ayala et al., 2014). Superoxide dismutase (SOD) prevented the expansion of oxidative free radical chain reaction and was an important line of defense for the oxygen-free radical scavenging system in organisms (Bresciani et al., 2015). The effects of Mdivi-1 on the levels of MDA and SOD in heart and vascular smooth muscle tissue were further observed. ...
Article
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Sepsis-associated organ dysfunction plays a critical role in its high mortality, mainly in connection with mitochondrial dysfunction. Whether the inhibition of mitochondrial fission is beneficial to sepsis-related organ dysfunction and underlying mechanisms are unknown. Cecal ligation and puncture induced sepsis in rats and dynamic related protein 1 knockout mice, lipopolysaccharide-treated vascular smooth muscle cells and cardiomyocytes, were used to explore the effects of inhibition of mitochondrial fission and specific mechanisms. Our study showed that mitochondrial fission inhibitor Mdivi-1 could antagonize sepsis-induced organ dysfunction including heart, vascular smooth muscle, liver, kidney, and intestinal functions, and prolonged animal survival. The further study showed that mitochondrial functions such as mitochondrial membrane potential, adenosine-triphosphate contents, reactive oxygen species, superoxide dismutase and malonaldehyde were recovered after Mdivi-1 administration via improving mitochondrial morphology. And sepsis-induced inflammation and apoptosis in heart and vascular smooth muscle were alleviated through inhibition of mitochondrial fission and mitochondrial function improvement. The parameter trends in lipopolysaccharide-stimulated cardiomyocytes and vascular smooth muscle cells were similar in vivo . Dynamic related protein 1 knockout preserved sepsis-induced organ dysfunction, and the animal survival was prolonged. Taken together, this finding provides a novel effective candidate therapy for severe sepsis/septic shock and other critical clinical diseases.
... Several research groups have proved that heavy metals can upset the oxidant-antioxidant balance with consequent generation and aggregation of free radicals and, eventually, oxidative stress [6,10]. Oxidative stress is a state that arises from the disequilibrium between the formation of free radicals and antioxidant defenses [56]. SOD and CAT are considered the first line of protection in the antioxidant system, which serves as a scavenger for free radicals [57]. ...
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The present study aimed to assess the potential protective effects of cinnamon (Cinnamomum zeylanicum, Cin) and probiotic against CuSO4-induced nephrotoxicity in broiler chickens. One-day-old Cobb chicks were assigned into seven groups (15 birds/group): control group, fed basal diet; Cin group, fed the basal diet mixed with Cin (200 mg/kg); PR group, receiving PR (1 g/4 L water); Cu group, fed the basal diets mixed with CuSO4 (300 mg/kg); Cu + Cin group; Cu + PR group; and Cu + Cin + PR group. All treatments were given daily for 6 weeks. Treatment of Cu-intoxicated chickens with Cin and/or PR reduced (p < 0.05) Cu contents in renal tissues and serum levels of urea, creatinine, and uric acid compared to the Cu group. Moreover, Cin and PR treatment decreased lipid peroxidation and increased antioxidant enzyme activities in chickens’ kidney. Additionally, significant reduction (p < 0.05) in the mRNA expression of tumor necrosis factor alpha (TNF-α), interleukin (IL-2) and Bax, and in cyclooxygenase (COX-II) enzyme expression, and significant elevation (p < 0.05) in mRNA expression of IL-10 and Bcl-2 were observed in kidneys of Cu + Cin, Cu + PR, and Cu + Cin + PR groups compared to Cu group. Conclusively, Cin and/or PR afford considerable renal protection against Cu-induced nephrotoxicity in chickens.
... Antioxidants can eliminate a little amount of ROS in the normal physiological situation, but in pathological conditions for example in diabetes, because of the excessive ROS production, antioxidants cannot remove ROS and therefore induce insult to heart cells [79]. It is revealed that the activity of SOD, one of the most significant antioxidant enzymes [80], markedly decreased following DCM. Pretreatment with doses of 50, 100, and 200 mg/kg of hawthorn leaf flavonoids (HLF) for 16 weeks significantly increased the activity of SOD and decreased the increased levels of MDA in underlying DCM [81]. ...
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Diabetes mellitus (DM) is one of the most important metabolic disorders associated with chronic hyperglycemia and occurs when the body cannot manage insulin secretion, insulin action, or both. Autoimmune destruction of pancreatic beta cells and insulin resistance are the major pathophysiological factors of types 1 and 2 of DM, respectively. Prolonged hyperglycemia leads to multiple organs dysfunctions, including nephropathy, neuropathy, cardiomyopathy, gastropathy, and micro- and macrovascular disorders. The basis of the metabolic abnormalities in carbohydrate, fat, and protein in diabetes is insufficient action of insulin on various target tissues. Medicinal plants are rich sources of bioactive chemical compounds with therapeutic effects. The beneficial effects of leaves, fruits, and flowers extracts of Crataegus oxyacantha, commonly called hawthorn, belonging to the Rosaceae family, are widely used as hawthorn-derived medicines. Data in this review have been collected from the scientific articles published in databases such as Science Direct, Scopus, PubMed, Web of Science, and Scientific Information Database from 2000 to 2021. Based on this review, hawthorn extracts appear both therapeutic and protective effects against diabetic-related complications in various organs through molecular mechanisms, such as decreasing triglyceride, cholesterol, very low density lipoprotein and increasing the antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, total antioxidant capacity, decreasing malondialdehyde level, and attenuating tumor necrosis factor alpha, interleukin 6 and sirtuin 1/AMP-activated protein kinase (AMPK)/nuclear factor kappa B (NF-κB) pathway and increasing the phosphorylation of glucose transporter 4, insulin receptor substrate 1, AKT and phosphoinositide 3-kinases, and attenuating blood sugar and regulation of insulin secretion, insulin resistance, and improvement of histopathological changes in pancreatic beta cells. Collectively, hawthorn can be considered as one new target for the research and development of innovative drugs for the prevention or treatment of DM and related problems.
... Antioxidants play a key role in controlling cardiopulmonary inflammation and fibrosis [116]. Plant-derived natural antioxidant vitamin A, C, and E from fruits, vegetables, beverages, and cereals [117][118][119][120], and synthetic antioxidant ascorbic acid/vitamin C, glutathione, uric acid, carotenes [121][122][123], and superoxide dismutase (enzyme) are known to suppress oxidative stress [124,125]-induced free radicals (ROS) as well as TGF-β, ERK, and NFκB-mediated signaling, thereby inhibiting fibrogenesis [126] (Figure 4). ...
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Advancements in cancer therapy increased the cancer free survival rates and reduced the malignant related deaths. Therapeutic options for patients with thoracic cancers include surgical intervention and the application of chemotherapy with ionizing radiation. Despite these advances, cancer therapy-related cardiopulmonary dysfunction (CTRCPD) is one of the most undesirable side effects of cancer therapy and leads to limitations to cancer treatment. Chemoradiation therapy or immunotherapy promote acute and chronic cardiopulmonary damage by inducing reactive oxygen species, DNA damage, inflammation, fibrosis, deregulation of cellular immunity, cardiopulmonary failure, and non-malignant related deaths among cancer-free patients who received cancer therapy. CTRCPD is a complex entity with multiple factors involved in this pathogenesis. Although the mechanisms of cancer therapy-induced toxicities are multifactorial, damage to the cardiac and pulmonary tissue as well as subsequent fibrosis and organ failure seem to be the underlying events. The available biomarkers and treatment options are not sufficient and efficient to detect cancer therapy-induced early asymptomatic cell fate cardiopulmonary toxicity. Therefore, application of cutting-edge multi-omics technology, such us whole-exome sequencing, DNA methylation, whole-genome sequencing, metabolomics, protein mass spectrometry and single cell transcriptomics, and 10 X spatial genomics, are warranted to identify early and late toxicity, inflammation-induced carcinogenesis response biomarkers, and cancer relapse response biomarkers. In this review, we summarize the current state of knowledge on cancer therapy-induced cardiopulmonary complications and our current understanding of the pathological and molecular consequences of cancer therapy-induced cardiopulmonary fibrosis, inflammation, immune suppression, and tumor recurrence, and possible treatment options for cancer therapy-induced cardiopulmonary toxicity.
... Aerobic exercise reduces oxidative stress by increasing the bioavailability of NO, thereby effectively preventing the occurrence of hypertension and cardiovascular disease (Korsager Larsen and Matchkov, 2016). SOD represents a group of enzymes that catalyze the dismutation of O2 − and the formation of H 2 O 2 , which is the major defense against superoxide radicals (Bresciani et al., 2015). Numerous studies in animals and humans have shown that aerobic exercise increases antioxidant enzyme activity, such as SOD and GPX, in the body or in tissues. ...
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Background: Oxidative stress (OS) plays an important role in the progression of many aging-related diseases. Exercises can delay this kind of progress, but aerobic exercise is the most commonly used type of training among older adults; therefore, its influence needs to be further verified. Methods: A literature search was conducted in eight electronic databases, including Cochrane, EMBASE, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Date, and SinoMed from their inception to April 2020. Methodological quality was assessed using Cochrane RoB tool v2.0 for individual studies, and RevMan 5.3 software was used to perform the meta-analysis. Results: The meta-analysis included 20 studies, involving 1,170 older adults. The results showed that regular aerobic exercise could reduce blood oxidant markers, including malondialdehyde (MDA; SMD=−1.80, 95% CI −2.46 to −1.14, p <0.001) and lipid peroxide (LPO; SMD=−1.12, 95% CI −2.03 to −0.22, p =0.02), and increase the levels of antioxidant factors, such as nitric oxide (NO; SMD=0.89, 95% CI 0.37–1.41, p <0.001), superoxide dismutase (SOD; SMD=0.63, 95% CI 0.25–1.01, p =0.001), and total antioxidant capacity (TAC; SMD=1.22, 95% CI 0.45–1.98, p =0.002), with clear statistical significance. It may also improve the levels of other OS markers, such as 8-OHdG, 8-isoPGF2, VE, and reduced glutathione/oxidized glutathione (GSH/GSSG). Conclusion: Regular aerobic exercise may have a positive effect on the OS levels of older adults by reducing some oxidant markers and increasing antioxidant marker levels.
... The nonenzymatic antioxidant system consists of plentiful antioxidant molecules, such as the reduced glutathione (GSH), [55] carotenoids, vitamins C/E, which can prevent oxidative damage by straightly neutralizing or quenching ROS. [56][57][58] The enzymatic antioxidant systems include the CAT, SOD, GPx, and thioredoxin-related family and play essential roles for ROS detoxification. As the highest POD content in mammalian cells, the CAT can efficiently convert H 2 O 2 into H 2 O and O 2 . ...
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In human systems, reactive oxygen species (ROS) significantly affect different physiological activities and play critical roles in diverse living processes. It is widely known that excessive ROS generation in inflammatory tissues can further deteriorate the localized tissue injury and cause chronic diseases. Though promising for reducing ROS levels, many antioxidant molecules and natural enzymes suffer from abundant intrinsic limitations. Recently, a series of biocatalytic or antioxidant nanostructures have been designed with distinctive ROS scavenging capabilities, which show promising activities to overcome these kernel challenges. In this timely review, the most recent advances in engineering biocatalytic and antioxidant nanostructures for ROS scavenging are summarized. First, the ROS scavenging principles and corresponding methods for testing various enzymatic activities are carefully concluded. Subsequently, the rationally designed nanostructures with high ROS scavenging efficiencies are comprehensively discussed, especially on the catalytic activities, mechanisms, and structure‐function relationships. After that, the representative applications of these ROS scavenging nanostructures for diverse biotherapeutics are summarized in detail. At last, the primary challenges and future perspectives in this emerging research frontier have also been outlined. It is believed that this progress review will offer a cutting‐edge understanding and guidance to engineering future high‐performance ROS scavenging nanostructures for broad biotherapeutic applications.
... The role of Mn in regulation of redox homeostasis, especially in mitochondria, is also mediated by mitochondrial MnSOD [106]. However, data on the association between Mn exposure and MnSOD activity are highly variable. ...
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Understanding of the immediate mechanisms of Mn-induced neurotoxicity is rapidly evolving. We seek to provide a summary of recent findings in the field, with an emphasis to clarify existing gaps and future research directions. We provide, here, a brief review of pertinent discoveries related to Mn-induced neurotoxicity research from the last five years. Significant progress was achieved in understanding the role of Mn transporters, such as SLC39A14, SLC39A8, and SLC30A10, in the regulation of systemic and brain manganese handling. Genetic analysis identified multiple metabolic pathways that could be considered as Mn neurotoxicity targets, including oxidative stress, endoplasmic reticulum stress, apoptosis, neuroinflammation, cell signaling pathways, and interference with neurotransmitter metabolism, to name a few. Recent findings have also demonstrated the impact of Mn exposure on transcriptional regulation of these pathways. There is a significant role of autophagy as a protective mechanism against cytotoxic Mn neurotoxicity, yet also a role for Mn to induce autophagic flux itself and autophagic dysfunction under conditions of decreased Mn bioavailability. This ambivalent role may be at the crossroad of mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis. Yet very recent evidence suggests Mn can have toxic impacts below the no observed adverse effect of Mn-induced mitochondrial dysfunction. The impact of Mn exposure on supramolecular complexes SNARE and NLRP3 inflammasome greatly contributes to Mn-induced synaptic dysfunction and neuroinflammation, respectively. The aforementioned effects might be at least partially mediated by the impact of Mn on α-synuclein accumulation. In addition to Mn-induced synaptic dysfunction, impaired neurotransmission is shown to be mediated by the effects of Mn on neurotransmitter systems and their complex interplay. Although multiple novel mechanisms have been highlighted, additional studies are required to identify the critical targets of Mn-induced neurotoxicity.
... Superoxide dismutases are a family of metal ion cofactor-requiring enzymes that function to precisely catalyze the dismutation of reactive superoxide anions into a more stable and readily diffusible H 2 O 2 (Zelko et al., 2002). Among these, superoxide dismutase 2 (SOD2) is found exclusively within the mitochondria (Bresciani et al., 2015). The critical importance of this ROS scavenging enzyme was confirmed by the extremely short lifespan of homozygous SOD2 knockout mice which die within weeks from severe dilated cardiomyopathy and exhibit hypothermia, growth retardation, metabolic disruption, and lipid accumulation in the liver (Li et al., 1995). ...
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Compelling evidence support an involvement of oxidative stress and intestinal inflammation as early events in the predisposition and development of obesity and its related comorbidities. Here we show that deficiency of the major mitochondrial antioxidant enzyme superoxide dismutase 2 (SOD2) in the gastrointestinal tract drives spontaneous obesity. Intestinal epithelium-specific Sod2 ablation in mice induced adiposity and inflammation via phospholipase A2 (PLA2) activation and increased release of omega-6 polyunsaturated fatty acid arachidonic acid. Remarkably, this obese phenotype was rescued when fed an essential fatty acid deficient diet, which abrogates de novo biosynthesis of arachidonic acid. Data from clinical samples revealed that the negative correlation between intestinal SOD2 mRNA levels and obesity features appears to be conserved between mice and humans. Collectively, our findings suggest a role of intestinal SOD2 levels, PLA2 activity and arachidonic acid in obesity presenting new potential targets of therapeutic interest in the context of this metabolic disorder.
... MnSOD2 reflects antioxidant enzyme activity, and it can protect cells from oxidative damage by clearing oxygenic radical. 25 Our study demonstrated that high uric acid levels increase MnSOD2 transcription, while fasudil and ROCK1 siRNA down-regulate MnSOD2 mRNA expression. However, Hong et al. 26 noted that high uric acid decreases total superoxide dismutase (T-SOD) activity. ...
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Introduction Oxidative stress is a pathologic feature of hyperuricemia that is highly prevalent and that contributes to kidney tubular interstitial fibrosis. Rho-kinase is closely related to mitochondrial-induced oxidative stress. Herein, we designed a study to explore the expression and role of Rho-kinase in hyperuricemia nephropathy. The secondary objective was to investigate whether the Rho-kinase signaling pathway regulates hyperuricemic tubular oxidative injury and apoptosis via the mitochondrial pathway in addition to the mechanisms that are involved. Materials and methods HK-2 cells were divided into the following five groups: normal; uric acid (UA); UA+Fasudil; UA+ROCK1 si-RNA; and UA+sc-siRNA. Rho-kinase activity, mitochondrial oxidative injury, and apoptosis-related protein levels were measured in each group. A t-test was used to analyze the difference between groups. Results Myosin phosphatase target subunit 1 (MYPT1) overexpression was shown in HK-2 cells, which was caused by UA. High concentrations of UA also up-regulated Rho-kinase expression and mitochondrial and apoptosis-related protein expression, while treatment with fasudil and ROCK1 si-RNA significantly attenuated these responses. Conclusion The Rho-kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis via regulating mitochondrial dyneins/biogenic genes in UA nephropathy, which suggests that the mitochondrial pathway might be a potential therapeutic target for hyperuricemia nephropathy.
... MDA is a stable product of lipid peroxidation, and the level of MDA is generally considered as a marker of oxidative stress, and high glucose can also induce an increase in MDA content [34][35][36]. The SOD family plays an important role in the regulation of oxidative stress, and the activity of SOD is decreased in a high-glucose environment [37,38]. In this experiment, we found that HG/HF increased the levels of ROS and MDA and reduced the level of SOD, but honokiol reversed the effect of HG/HF on cells. ...
Article
Honokiol plays an important role in anti-oxidation, but its role in diabetic vascular complications is unclear. In this study, the effects of honokiol in high glucose/high fat (HG/HF)-induced human umbilical vein endothelial cells (HUVECs) were explored. After pre-treatment with honokiol, the cells were transferred to an HG/HF medium, and cell viability and apoptosis were respectively measured by methyl tetrazolium and flow cytometry. Moreover, the contents of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) were measured. The expressions of C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), phosphorylated-protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), phosphorylated-inositol requiring enzyme-1α (p-IRE1α), cleaved caspase-3 and SIRT1 were determined by Western blot or quantitative real-time PCR, respectively. Finally, the viability, apoptosis, and the contents of ROS, MDA, and SOD, as well as the expressions of CHOP, GRP78, p-PERK, p-IRE1α, cleaved caspase-3, Akt, p-Akt, and SIRT1 in the cells transfected with small interfering RNA SIRT1 (siSIRT1) were detected by the previously mentioned methods. Honokiol reversed the effect of HG/HF on promoting cell apoptosis, ROS and MDA contents, and the expressions of CHOP, GRP78, p-PERK, p-IRE1α and cleaved caspase-3, and also reversed the inhibitory effect of HG/HF on cell viability, SOD content and SIRT1 expression. However, siSIRT1 reversed the above effects caused by honokiol. Honokiol activated SIRT1 promoter. SIRT1 interacted with Akt, consequently promoting the activity of Akt. Therefore, honokiol activates the Akt pathway by regulating SIRT1 expression to regulate endoplasmic reticulum stress, promotes cell viability and inhibits the apoptosis of HG/HF-induced HUVECs.
... Published data show that MTL can counterpart oxidative stress in liver cells by increasing SOD production and inhibiting ROS and MDA [6]. MTL also contains SOD (6667 U/100 ml) and manganese (0.022 mg/100 ml); those are important for alleviating the oxidative stress injury [20]. Thus, it is of significance to fractionate the substances to induce SOD in sPCs from MTL that may be conducted test (a, b) or Bonferroni's test (f-h). ...
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The infection of coronavirus disease (COVID-19) seriously threatens human life. It is urgent to generate effective and safe specific antibodies (Abs) against the pathogenic elements of COVID-19. Mice were immunized with SARS-CoV-2 spike protein antigens: S ectodomain-1 (CoV, in short) mixed in Alum adjuvant for 2 times and boosted with CoV weekly for 6 times. A portion of mice were treated with Maotai liquor (MTL, in short) or/and heat stress (HS) together with CoV boosting. We observed that the anti-CoV Ab was successfully induced in mice that received the CoV/Alum immunization for 2 times. However, upon boosting with CoV, the CoV Ab production diminished progressively; spleen CoV Ab-producing plasma cell counts reduced, in which substantial CoV-specific Ab-producing plasma cells (sPC) were apoptotic. Apparent oxidative stress signs were observed in sPCs; the results were reproduced by exposing sPCs to CoV in the culture. The presence of MTL or/and HS prevented the CoV-induced oxidative stress in sPCs and promoted and stabilized the CoV Ab production in mice in re-exposure to CoV. In summary, CoV/Alum immunization can successfully induce CoV Ab production in mice that declines upon reexposure to CoV. Concurrent administration of MTL/HS stabilizes and promotes the CoV Ab production in mice.
... In mammals, MnSOD is considered to operate as a stress-responsive factor. Its expression level could be influenced by environmental and biological stimuli, and its mutation or loss-of-activity is also lethal for aerobic organisms (Bresciani et al., 2015). Previous research in crustaceans also confirmed that cMnSOD is linked to the immune response to bacterial and viral infections (Liu et al., 2013;Wang et al., 2015). ...
Article
An excess of reactive oxygen species (ROS) usually disrupts the balance of the antioxidant system and impairs the homeostasis of cells, resulting in serious oxidative damage. Therefore, a better understanding of how the immune system protects itself against such excessive oxidative stress is crucial. SODs play an indispensable role in antioxidant defense and the innate immune system. Among those, MnSOD is one of the most being. Previous studies using crustaceans have focused much on the gene expression changes underlying pathogenic infections, which generally indicate that MnSOD is involved in the antibacterial immune process of crustaceans. Yet the detailed biological properties of MnSOD and mechanism by which it counters pathogen infection in Macrobrachium rosenbergii remain unclear. Here we first cloned the cytosolic MnSOD from M. rosenbergii (MrcMnSOD), and then analyzed its distribution in tissues and expression patterns under bacterial infection with Staphylococcus aureus and Vibrio parahaemolyticus. The results revealed MrcMnSOD widely distributed in the tested tissues, whose expression level was highest in the hepatopancreas, followed by the stomach and intestine. Infection with S. aureus and V. parahaemolyticus significantly up-regulated both total SOD activity and transcription level of MrcMnSOD. To further investigate the possible mechanism of MrcMnSOD's participation in that antibacterial immune response, an RNA knockdown assay in vivo was performed. After knocking down MrcMnSOD, a higher mortality rate and more residual bacteria in haemocytes were recorded than for control group. Furthermore, an in vitro bacterial agglutination assay of MrcMnSOD demonstrated MrcMnSOD harbors broad bacterial agglutination to both gram-negative and gram-positive bacteria. Overall, our findings strongly suggest that MrcMnSOD is only capable of modulating the host's redox state but also exerting an antibacterial function in M. rosenbergii, thus shedding new light on the immune functioning of MrcMnSOD in crustaceans. Importantly, this work provides a new perspective for disease prevention and control in farmed crustaceans.
... This finding raises the possibility of an important role of antioxidant function in modulating lifespan (Lucas and Keller, 2018). The EC-SOD could catalyze O 2 − anion dismutation into O 2 and H 2 O 2 , avoid excessive accumulation to produce toxicity (Bresciani et al., 2015). It is demonstrated in the animal model that the absence of EC-SOD was found to be without effect on the lifespan of mice, however, it might lead to a higher risk of oxidation-induced damage such as premature death under high oxygen tension. ...
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Background The dynamic balance between oxidation and anti-oxidation in the body’s internal environment has a significant meaning for human health. Physical exercise and antioxidative supplementation could affect the balance of oxidation and anti-oxidation systems. The evidence on the effects of physical exercise and antioxidative supplementation is mixed. Aims To identify the effects of physical exercise, antioxidative supplementation, and their combination on the dynamic balance between oxidation and anti-oxidation in different subgroups of healthy adults. Methods All studies which reported randomized controlled trials with healthy participants were screened and included from the databases of PubMed, Medline, Embase, and Ovid. All participants were reclassified according to their different daily life activities. All physical exercise interventions were reclassified according to the intensity. The effect size would be calculated in percent or factor units from the mean level change with its associated random-effect variance. Result There were 27 studies included in this review. The agreement between authors by using The Cochrane Collaboration Risk of Bias Assessment Tool reached a kappa-value of 0.72. Maintaining a regular physical exercise routine in an appropriate intensity would be beneficial to the body’s anti-oxidative potential. Anti-oxidative supplementation could have some positive but limited effects on the body’s anti-oxidative status and complex interaction with physical exercise. Conclusion Keeping a regular physical exercise routine and gradually increasing its intensity according to the individual’s daily life activity might be a better choice to maintain and enhancing the body’s antioxidation potential, only using anti-oxidative supplementation is not recommended. More research is needed to explore the best combination protocol. Registration Number CRD42021241995.
... It is well-established that the detoxification activity of antioxidant enzymes is dysregulated in tumors [1,2], implying that a loss of reactive oxygen species (ROS) buffer or detoxification activity corresponds to a more oncogenic and/or therapyresistant phenotypes [1][2][3]. In particular, Manganese superoxide dismutase (MnSOD) is an evolutionarily conserved protein that functions as a primary mitochondrial superoxide scavenger and is part of the superoxide dismutase family (SOD1-3), which catalyzes the conversion of superoxide molecules (O2 -) produced from mitochondrial respiration to H 2 O 2 [4][5][6][7] and diatomic oxygen [8,9]. The homotetrameric MnSOD, with four identical subunits each harboring a Ivyspring International Publisher Mn 2+ atom [10], is encoded in the nucleus and then translocated to the mitochondrial matrix where the targeting signal is cleaved post-translationally [11]. ...
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Manganese superoxide dismutase (MnSOD) acetylation (Ac) has been shown to be a key post-translational modification important in the regulation of detoxification activity in various disease models. We have previously demonstrated that MnSOD lysine-68 (K68) acetylation (K68-Ac) leads to a change in function from a superoxide-scavenging homotetramer to a peroxidase-directed monomer. Here, we found that estrogen receptor positive (ER+) breast cancer cell lines (MCF7 and T47D), selected for continuous growth in cisplatin (CDDP) and doxorubicin (DXR), exhibited an increase in MnSOD-K68-Ac. In addition, MnSOD-K68-Ac, as modeled by the expression of a validated acetylation mimic mutant gene (MnSODK68Q ), also led to therapy resistance to CDDP and DXR, altered mitochondrial structure and morphology, and aberrant cellular metabolism. MnSODK68Q expression in mouse embryo fibroblasts (MEFs) induced an in vitro transformation permissive phenotype. Computerized molecular protein dynamics analysis of both MnSOD-K68-Ac and MnSOD-K68Q exhibited a significant change in charge distribution along the α1 and α2 helices, directly adjacent to the Mn2+ binding site, implying that this decrease in surface charge destabilizes tetrameric MnSOD, leading to an enrichment of the monomer. Finally, monomeric MnSOD, as modeled by amber codon substitution to generate MnSOD-K68-Ac or MnSOD-K68Q expression in mammalian cells, appeared to incorporate Fe to maximally induce its peroxidase activity. In summary, these findings may explain the mechanism behind the observed structural and functional change of MnSOD-K68-Ac.
... Yi et al. reported that administration of MTL efficiently inhibited oxidative stress by increasing SOD in liver cells [23]. MTL also contains SOD (6667 U/100 mL) and manganese (0.022 mg/100 mL), which can counteract the oxidative stress [40]. ...
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Regulatory T cells (Treg) are known to have a central role in orchestrating immune responses, but less is known about the destiny of regulatory T cells after being activated by specific antigens (Ags). This study aimed to investigate the role of superoxide dismutase, an active molecule in the regulation of oxidative stress in the body, in the prevention of Treg apoptosis induced by specific Ags. Ag‐specific Tregs were isolated from the DO11.10 mouse intestine. A food allergy mouse model was developed with ovalbumin as the specific Ag and here, we observed that exposure to specific Ag induced Treg apoptosis through converting the precursor of TGF‐β to its mature form inside the Tregs. Oxidative stress was induced in Tregs upon exposure to specific Ags, in which Smad3 bound the latency‐associated peptide to induce its degradation, converting the TGF‐β precursor to its mature form, TGF‐β. Suppressing oxidative stress in Tregs alleviated the specific Ag‐induced Treg apoptosis in in vitro experiments and suppressed experimental food allergy by preventing the specific Ag‐induced Treg apoptosis in the intestine. In conclusion, exposure to specific Ags induces Treg apoptosis and it can be prevented by up‐regulating superoxide dismutase or suppressing reactive oxidative species in Tregs. This article is protected by copyright. All rights reserved
... SOD enzyme regulates the levels of superoxide and hydrogen peroxide produced by cells, and then regulates cell signal transduction. 19 Catalase is an important antioxidant and a marker enzyme of peroxisomes. It accounts for 40% of the total peroxisome enzymes. ...
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Purpose: Epigallocatechin-3-gallate (EGCG) is a major ingredient of catechin polyphenols and exerts protective effects because of its strong antioxidant properties. As far as we know, there is still a lack of systematic research on the effects of EGCG on the in vitro maturation (IVM) and in vitro fertilization (IVF) of porcine oocytes. The present study aimed to determine the effects of EGCG on the IVM and IVF of porcine oocytes. Methods: Porcine oocytes were treated with different concentrations of EGCG (5, 10 and 20 µM), and the cumulus cell expansion, oocyte maturation rate, reactive oxygen species (ROS), glutathione (GSH) and malondialdehyde (MDA) levels, total antioxidant capacity were determined. The mRNA expression levels of oxidative stress- and apoptosis-associated genes were determined by quantitative real-time PCR. The cleavage rate and blastocyst rate of oocytes after 10 μM EGCG treatment during IVM and IVF were also evaluated. Results: EGCG at 5, 10 and 20 μM significantly promoted cumulus cell expansion, and EGCG at 10 μM increased the oocyte maturation rate. EGCG (10 μM) treatment reduced the ROS and MDA levels, while increased the antioxidant capacity and GSH concentrations in the mature oocytes. The qRT-PCR results showed that EGCG treatment up-regulated the mRNA expression of catalase, glutathione peroxidase and superoxide dismutase in the mature oocytes. In addition, EGCG treatment also decreased the mRNA expression levels of Bax and caspase-3 and increased the Bcl-2 mRNA expression level in the mature oocytes. In addition, the cleavage rate and blastocyst rate of oocytes treated with 10 μM EGCG during IVM and IVF were significantly higher than those of the control group. Conclusion: Our results suggest that EGCG promotes the in vitro maturation and embryo development following IVF of porcine oocytes. The protective effects of EGCG on the oocytes may be associated with its antioxidant and anti-apoptosis properties.
... In our experiments, MDA was significantly increased in diabetic rats, which was consistent with previously reported findings [15], and GEP could lower the level of MDA. SOD, a main antioxidant enzyme, plays a role in the destruction of free superoxide radicals and blocks free radical-induced damage [33]. The SOD activity was significantly decreased in diabetic rat, while GEP could improve the activity of SOD. ...
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Background. Gastric electrical pacing (GEP) could restore interstitial cells of Cajal in diabetic rats. M2 macrophages contribute to the repair of interstitial cells of Cajal injury though secreting heme oxygenase-1 (HO-1). The aim of the study is to investigate the effects and mechanisms of gastric electrical pacing on M2 macrophages in diabetic models. Methods. Sixty male Sprague-Dawley rats were randomized into control, diabetic (DM), diabetic with the sham GEP (DM+SGEP), diabetic with GEP1 (5.5 cpm, 100 ms, 4 mA) (DM+GEP1), diabetic with GEP2 (5.5 cpm, 300 ms, 4 mA) (DM+GEP2), and diabetic with GEP3 (5.5 cpm, 550 ms, 4 mA) (DM+GEP3) groups. The apoptosis of interstitial cells of Cajal and the expression of macrophages were detected by immunofluorescence technique. The expression levels of the Nrf2/HO-1 and NF-κB pathway were evaluated using western blot analysis or immunohistochemical method. Malonaldehyde, superoxide dismutase, and reactive oxygen species were tested to reflect the level of oxidative stress. Results. Apoptosis of interstitial cells of Cajal was increased in the DM group but significantly decreased in the DM+GEP groups. The total number of macrophages was almost the same in each group. In the DM group, M1 macrophages were increased and M2 macrophages were decreased. However, M2 macrophages were dramatically increased and M1 macrophages were reduced in the DM+GEP groups. Gastric electrical pacing improved the Nrf2/HO-1 pathway and downregulated the phosphorylation of NF-κB. In the DM group, the levels of malonaldehyde and reactive oxygen species were elevated and superoxide dismutase was lowered, while gastric electrical pacing reduced the levels of malonaldehyde and reactive oxygen species and improved superoxide dismutase. Conclusion. Gastric electrical pacing reduces apoptosis of interstitial cells of Cajal though promoting M2 macrophages polarization to play an antioxidative stress effect in diabetic rats, which associates with the activated Nrf2/HO-1 pathway and the phosphorylation of NF-κB pathway. 1. Introduction For centuries, gastrointestinal motility disorders, one of the most frequently occurring diseases, have kept perplexed people’s lives with decades of diabetes mellitus [1]. Gastroparesis, namely delayed gastric emptying, is a disorder that slows or reduces the food transit from the stomach to the small intestine without mechanical obstruction. However, effective therapies for gastroparesis remain elusive with limited roles and side effects. Fortunately, nondrug treatments, such as electroacupuncture (EA) and gastric electrical stimulation (GES), are gradually taken seriously because of its apparent efficacy without side effects. In particular, long pulse GES, for it induces slow waves also referred to as gastric electrical pacing (GEP), has a direct impact on gastric motility. At present, GEP develops as an alternative therapy of gastroparesis, but the mechanisms underlying its efficacy remain unclear. Interstitial cells of Cajal (ICCs) serve as pacemakers and generate slow waves spontaneously in the stomach. Defect of ICCs has been consistently found in both humans and animal models with diabetic gastroparesis [2, 3]. We have reported that long-pulse GES could repair the injured ICCs partly by IGF-1 signaling pathway and enhancing the proliferation of ICCs [4, 5]. However, apoptosis of ICCs was also certificated in the stomach of gastroparesis [6]; the effects and mechanisms of GEP on apoptosis of ICCs need to be further clarified. Macrophages have two different phenotypes: proinflammatory M1 macrophages and anti-inflammatory M2 macrophages. They can be transformed into each other in a certain internal environment. Studies have shown that gastrointestinal motility disorder did not occur in diabetic mice with the absence of macrophages, suggesting that macrophages may participate in the development of gastroparesis [7]. It is also reported that phenotypic polarization of M2 macrophages could improve the delayed gastric emptying [8]. Further studies have shown that there was no significant change in the total number of macrophages in animal models and patients of diabetic gastroparesis, while CD206+ M2 macrophages were selectively decreased, accompanied by ICC deletion, resulting in delayed gastric emptying [9–11]. Accordingly, GEP may promote the phenotypic polarization of M2 macrophages to improve ICC expression and gastric emptying. Heme oxygenase-1 (HO-1) is a widely existing antioxidant defense enzyme, which is not expressed or low expressed in normal tissues, but upregulated during stress playing an anti-inflammatory, antioxidative, and antiapoptotic role. In the gastrointestinal tract, HO-1 is mainly produced and expressed by resident M2 macrophages [12]. Recently, in a study of diabetic gastroparesis model, it has been found that the downregulation of HO-1 could not resist oxidative stress injury, which leads to the destruction of ICCs network and delayed gastric emptying, but upregulation of HO-1 could repair the injury of ICCs and improve the delayed gastric emptying [13, 14]. Similarly, Tian LG et al. reported that the expression of HO-1 in gastric antrum of diabetic gastroparesis mice was significantly decreased, and EA could improve the expression of HO-1 and gastric motility [15]. Therefore, we speculate that GEP may play a key role in improving gastric motility disorder by upregulating HO-1 to repair ICC injury. Also, studies have shown that HO-1 can protect and reverse oxidative stress damage to ICCs [13]. Stem cell factor (also known as SCF, c-kit ligand) is essential for survival and maintenance of ICCs, but there are few reports about the correlation between HO-1 and SCF. Recent studies [16] have shown that the NF-κB signaling pathway was activated in diabetic gastrointestinal motility disorders and the decrease expression of SCF/c-kit causes the increase of ICC apoptosis, suggesting that the activation of NF-κB signaling may be an important factor in ICC apoptosis. It is also reported that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in defending against inflammation in different tissues via activation of phase II enzyme HO-1 and inhibition of the NF-κB signaling pathway [17]. Other studies [18] have shown that HO-1 can inhibit the phosphorylation of NF-κB p65, promote the binding of anti-apoptotic genes to NF-κB, and promote gene transcription to play an antiapoptotic role. In addition, studies in human lung fibroblasts have shown that nuclear transcription factor NF-κB binds to enhancers of SCF gene and promotes SCF transcription [19]. We assumed that HO-1 may play an antiapoptotic role by inhibiting the phosphorylation of NF-κB p65. In this study, we aimed to explore the effects of GEP on ICC apoptosis and phenotypic polarization of macrophages and to investigate the possible mechanisms of renovation of ICC injury in diabetic rats. 2. Materials and Methods 2.1. Animals Male Sprague-Dawley rats (weighing 160-200 g, ) were purchased from Jinan Pengyue Experimental Animal Breeding Co. Ltd. (Shandong, China) and were kept in the suitable laboratory conditions (22-23°C, 12/12 h light-dark cycle) with food and water ad libitum. The experimental procedures were implemented, following the ethical guidelines from the Animal Care and Use Committee of Binzhou Medical University Hospital Laboratory Animal Ethical Committee. The rats were randomly divided into the normal control, diabetes (DM), diabetic+sham GEP (DM+SGEP), and diabetic+GEP (DM+GEP) groups (Figure 1).
... These enzymes assist cells in fixing cellular membranes injured by ROS. In particular, SOD converts the excess of superoxide anions into H 2 O 2 , which is then removed by GSH and CAT [61,62]. Resveratrol administration reduced lipid peroxidation and increased GSH, CAT and SOD activities, helping the antioxidant defense system to neutralize the excess of free radicals associated with pain. ...
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Low back pain (LBP) management is an important clinical issue. Inadequate LBP control has consequences on the mental and physical health of patients. Thus, acquiring new information on LBP mechanism would increase the available therapeutic tools. Resveratrol is a natural compound with many beneficial effects. In this study, we investigated the role of resveratrol on behavioral changes, inflammation and oxidative stress induced by LBP. Ten microliters of Complete Freund’s adjuvant (CFA) was injected in the lumbar intervertebral disk of Sprague Dawley rats to induce degeneration, and resveratrol was administered daily. Behavioral analyses were performed on day zero, three, five and seven, and the animals were sacrificed to evaluate the molecular pathways involved. Resveratrol administration alleviated hyperalgesia, motor disfunction and allodynia. Resveratrol administration significantly reduced the loss of notochordal cells and degenerative changes in the intervertebral disk. From the molecular point of view, resveratrol reduced the 5th/6th lumbar (L5–6) spinal activation of the WNT pathway, reducing the expression of WNT3a and cysteine-rich domain frizzled (FZ)8 and the accumulation of cytosolic and nuclear β-catenin. Moreover, resveratrol reduced the levels of TNF-α and IL-18 that are target genes strictly downstream of the WNT/β-catenin pathway. It also showed important anti-inflammatory activities by reducing the activation of the NFkB pathway, the expression of iNOS and COX-2, and the levels of PGE2 in the lumbar spinal cord. Moreover, resveratrol reduced the oxidative stress associated with inflammation and pain, as shown by the observed reduced lipid peroxidation and increased GSH, SOD, and CAT activities. Therefore, resveratrol administration controlled the WNT/β-catenin pathway and the related inflammatory and oxidative alterations, thus alleviating the behavioral changes induced by LBP.
... SOD is the first line of defense among antioxidant enzymes against oxygen free radicals, catalyzing the dismutation of the superoxide anion in oxygen (O 2 ) and hydrogen peroxide (H 2 O 2 ), which is less reactive, thus preventing the generation of highly reactive OH radicals. 39 The SOD activity, both for OVX and SHAM animals, did not differ between the animals that consumed SD and HFD (SD + CC × HFD + CC) and between the animals that consumed SD + CC and SD + chia (SD + CC × SD + chia). Among the OVX animals that consumed HFD (HFD + CC × HFD + chia), those that consumed chia showed higher levels of SOD than those that did not consume chia. ...
Article
The estrogen reduction is associated with the increased risk factors for cardiovascular disease development. The present study aimed to evaluate the effect of chia consumption in a standard diet (SD) or high fat diet (HFD) on ovariectomized (OVX) and non-ovariectomized (SHAM) rats, in relation to biometric measurements, oxidative stress, mineral content and ATPase enzymes of the heart. The study was conducted with 80 female Wistar rats, which received SD or HFD for 18 weeks. During the first 7 weeks, the animals received SD or HFD. Then, 40 rats were ovariectomized and 40 rats were SHAM operated. After recovery from surgery, the animals were allocated into 8 groups (n = 10) and received the following diets: SD, SD + chia, HFD and HFD + chia, for 8 weeks. In the OVX group, HFD increased weight gain, adiposity, cardiac hypertrophy, nitric oxide (NO) and K concentration and decreased Na+/K+ATPase activity. In association with HFD, ovariectomy decreased catalase activity, Mg, Cu and Zn concentration, total ATPase activity, Na+/K+ATPase and Mg2+ATPase, this group also presented higher NO, Ca, K, Fe and Mn concentration in the heart. The SHAM group fed chia presented lower fat content in the heart. In the OVX group fed HFD, chia increased the activity of superoxide dismutase, decreased NO and maintained the content of minerals and ATPase enzymes. Thus, chia improved the biometric parameters of the heart, the antioxidant activity and maintained the content of minerals and ATPase enzymes, showing a cardioprotective action, but without reversing the ovariectomy deleterious effects.
... He et al. demonstrated that the overexpression of YB-1 could significantly increase the expression levels of IL-8 in S. chuatsi, indicating that YB-1 induced the NF-κB signaling pathway (He et al. 2019). There are three SOD isoenzymes, including copper/zinccontaining SOD (Cu-ZnSOD or SOD1), which is mainly cytosolic, a manganese SOD in mitochondria (MnSOD or SOD2) (Bresciani et al. 2015). To further dissect the potential mechanism of LmYB-1 involvement in anti-oxidation activities, we examined the effects of LmYB-1 on gene expression of SOD. ...
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Thesis
L’insuffisance cardiaque (IC) est une cause majeure de mortalité dans les pays industrialisés. Bien que les mécanismes intrinsèques de l’IC soient complexes, il a été démontré que le stress oxydant était un déterminant essentiel dans la progression de la dysfonction ventriculaire au cours de la pathologie. En ce sens, l’équipe s’est intéressée à la monoamine oxydase A (MAO-A), une enzyme située au niveau de la membrane externe mitochondriale, qui constitue la principale voie de dégradation des catécholamines et de la sérotonine. Au cours des dernières années, la MAO-A a été identifiée comme une source importante de stress oxydant dans le cœur. Le but de cette thèse a été de mieux caractériser les mécanismes d’action de la MAO-A, du stress oxydant et de ses effecteurs dans l’altération cardiaque, ce qui pourrait constituer une avancée importante dans la compréhension des mécanismes physiopathologiques de l’IC. Dans une première partie, nous nous sommes intéressés à l’infarctus du myocarde (IDM) chronique qui constitue la cause principale d’IC. Nous avons observé que la MAO-A était activée au cours de l’ischémie chronique chez des patients ainsi que chez des souris, et que cette activation participait au remodelage délétère post-IDM. D’un point de vue mécanistique, nous avons montré que l’activation de la MAO-A favorisait l’accumulation mitochondriale de 4-hydroxynonénal (4-HNE), un aldéhyde très réactif, via une peroxydation lipidique intra-mitochondriale. Cette accumulation a conduit à la fixation du 4-HNE sur certaines cibles mitochondriales, favorisant une surcharge calcique dans l’organite, une altération de la chaîne respiratoire et un déficit énergétique, qui participent au remodelage délétère post-IDM. Cette étude a donc permis de mettre en évidence le rôle clé de la dysfonction mitochondriale dans les dommages induits par la MAO-A. Dans une deuxième partie, nous avons cherché à caractériser les conséquences de la suractivation de la MAO-A sur le contrôle qualité mitochondrial à long terme. Les mitochondries dysfonctionnelles sont normalement éliminées par la voie autophagie-lysosome, mais des études ont montré que cette voie était progressivement altérée dans l’IC. Nos travaux ont montré que l’activation chronique de la MAO-A entrainait une altération de l’acidification lysosomale et un défaut de translocation nucléaire du facteur de transcription EB (TFEB), un « master régulateur » de l'autophagie et de la biogenèse des lysosomes.
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A total of 649 children aged 7–13 years of age were recruited in a cross-sectional study in Tongxu County, China (2017) to assess the effects of interaction between single nucleotide polymorphisms (SNPs) in SOD2 and SOD3 gene and fluoride exposure on dental fluorosis (DF) status. Associations between biomarkers and DF status were evaluated. Logistic regression suggested that the risk of DF in children with rs10370 GG genotype and rs5746136 TT genotype was 1.89-fold and 1.72-fold than that in children with TT/CC genotype, respectively. Increased T-SOD activity was associated with a lower risk of DF (OR = 0.99). The rs2855262*rs10370*UF model was regarded as the optimal interaction model in generalized multifactor dimensionality reduction analyses. Our findings suggested that rs4880 and rs10370 might be useful genetic markers for DF, and there might be interactions among rs10370 in SOD2, rs2855262 in SOD3, and fluoride exposure on DF status.
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Acute ischemic stroke (AIS) is the primary reason for sustained disability and the second leading cause of death worldwide. Multiple complex mechanisms contribute to the pathophysiology of AIS leading to disruptions in synaptic signalling and plasticity. Two key interrelating features of cerebral ischemia include the reduction in oxygen and glucose availability and oxidative damage. During ischemia, oxygen deprivation causes several adaptive changes including the stabilisation of neuroprotective hypoxia-inducible factors (HIFs). HIF activity is regulated by oxygen-dependent hydroxylases termed prolyl-4-hydroxylase domain enzymes (PHDs) and can be pharmacologically activated with PHD inhibitors. Preconditioning the HIF system with PHD inhibitors in in vitro ischemic models such as oxygen-glucose deprivation (OGD) has demonstrated neuroprotective effects on synaptic transmission and modulatory effects on synaptic plasticity. Restoration of blood flow as quickly as possible remains the gold-standard for all current therapeutic approaches to stroke. However, rapid recanalization is associated with major complications, of which cerebral ischemia-reperfusion injury (I-RI) is one of the most severe. I-RI results in oxidative damage leading to the neurotoxic overproduction of reactive oxygen species. Antioxidant treatments have shown positive effects in-vitro but some of which show modulatory effects on synaptic plasticity. Therefore, a greater knowledge of the exact mechanisms involved in ischemia/aglycemia and oxidative damage during AIS is a priority in order to arrive at a better understanding of how they can be targeted for neuroprotection. This review focuses on the response of neurons to HIF and its targets, including PHD enzymes and preconditioning with PHD inhibitors. We also discuss the modulation of synaptic transmission with antioxidants and how they both contribute to and modulate synaptic plasticity.
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Soybean [ Glycine max (L.) Merrill] is a predominant edible plant and a major supply of plant protein worldwide. Global demand for soybean keeps increasing as its seeds provide essential proteins, oil, and nutraceuticals. In a quest to meet heightened demands for soybean, it has become essential to introduce agro-technical methods that promote adaptability to complex environments, improve soybean resistance to abiotic stress , and increase productivity. Plant growth regulators are mainly exploited to achieve this due to their crucial roles in plant growth and development. Increasing research suggests the influence of plant growth regulators on soybean growth and development, yield, quality, and abiotic stress responses. In an attempt to expatiate on the topic, current knowledge, and possible applications of plant growth regulators that improve growth and yield have been reviewed and discussed. Notably, the application of plant growth regulators in their appropriate concentrations at suitable growth periods relieves abiotic stress thereby increasing the yield and yield components of soybean. Moreover, the regulation effects of different growth regulators on the morphology, physiology, and yield quality of soybean are discoursed in detail.
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Manganese management in plant cells is important for providing cells with appropriate development conditions, as both manganese deficiency and excess interfere with redox homeostasis and activate oxidative stress in cells. Excessive amounts of Mn affect morphological and anatomical parameters but the precise mechanism of manganese toxicity has not been fully understood yet. This review presents the impact of Mn on plant metabolism. We discuss the role of this element in the reduction and oxidation, as well as the alterations appearing in the cells as a result of excessive accumulation of manganese. The closest attention is paid to the transport of Mn into the cells and its interaction with other essential elements. We also summarize the observed alterations in physiological and biochemical properties of plant cells, with regard to the influence of Mn on defense mechanism initiated in its presence. Finally, this review recapitulates possible cell defense strategies under excessive manganese accumulation.
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In celebration of the centenary of the National Institute of Nutrition (NIN), Hyderabad, India (1918-2018), a symposium highlighted the progress in nutrition knowledge made over the century, as well as major gaps in implementation of that knowledge. Brain famine caused by a shortage of nutrients required for perinatal brain development has unfortunately become a global reality, even as protein-calorie famine was largely averted by the development of high yield crops. While malnutrition remains widespread, the neglect of global food policies that support brain development and maintenance are most alarming. Brain disorders now top the list of the global burden of disease, even with obesity rising throughout the world. Neurocognitive health, remarkably, is seldom listed among the non-communicable diseases (NCDs) and is therefore seldom considered as a component of food policy. Most notably, the health of mothers before conception and through pregnancy as mediated by proper nutrition has been neglected by the current focus on early death in non-neurocognitive NCDs, thereby compromising intellectual development of the ensuing generations. Foods with balanced essential fatty acids and ample absorbable micronutrients are plentiful for populations with access to shore-based foods, but deficient only a few kilometres away from the sea. Sustained access to brain supportive foods is a priority for India and throughout the world to enable each child to develop to their intellectual potential, and support a prosperous, just, and peaceful world. Nutrition education and food policy should place the nutritional requirements for the brain on top of the list of priorities.
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Diabetic retinopathy (DR) is the most typical complication of diabetes, which severely threatens sight. Tribbles homolog 3 (TRB3), a kind of pseudokinase, is discovered to be highly expressed in diabetes and retinas after retinal detachment. TRB3 expression in human retinal pigment epithelial (hRPE) cells exposed to different concentrations of glucose was tested by RT-qPCR and western blot. Then, cells were induced with 30 mM high glucose (HG) to establish a DR cell model. Following TRB3 knockdown, cell viability estimation employed CCK-8 assay. The mRNA levels of inflammatory factors were detected by RT-qPCR. Reactive oxygen species (ROS) level was measured by DCFH-DA assay, and levels of oxidative stress markers were evaluated applying corresponding kits. Cell apoptosis was assayed by TUNEL assay and western blot. Following, the growth factor receptor-bound 2 (GRB2) expression was also examined by RT-qPCR and western blot. The interaction between TRB3 and GRB2 was verified by Co-IP assay. After GRB2 was overexpressed in HG-induced hRPE cells transfected with shRNA-TRB3, functional experiments were conducted again. The results manifested that TRB3 expression was elevated under HG conditions. Deficiency of TRB3 enhanced the viability while alleviated inflammation, oxidative stress, and apoptosis in HG-induced hRPE cells. GRB2 was also increased in HG-exposed hRPE cells. Moreover, GRB2 had a strong affinity with TRB3 and positively regulated by TRB3. After GRB2 overexpression, the effects of TRB3 knockdown on HG-stimulated hRPE cells were all reversed. Briefly, this study confirmed the promoting role of TRB3/GRB2 axis in the progression of DR.
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In this research, two new 1D coordination polymers of Mn(II), [Mn(LH)2(µ1,5-dca)2]n (1) and [Mn(LH)2(µ1,3-N3)(CH3OH)(N3)]n (2) were synthesized and characterized by elemental analysis, spectroscopic methods, single crystal X-ray analysis and magnetic measurements (LH = 1-[(E)-(5-chloro-2-pyridyl)iminiomethyl]-2-naphtholate). These compounds were synthesized by the reaction of LH, MnCl2·4H2O and NaN(CN)2 (for compound 1) or NaN3 (for compound 2) in 1:1:2 M ratio in methanol. The spectroscopic and structural studies indicated that strong intramolecular proton transfer from naphtholic oxygen to the imine nitrogen is occurred in the ligand and due to this; the nitrogen atom of imine functionality is not coordinated to the metal core. As a result, the ligand is coordinated to the metal core as monodentate neutral ligand. The proton transfer process was attributed to the strong electron withdrawing properties of 5-chloropyridine ring. In the structure of compound 1 and 2, the manganese ions are connected to each other through µ1,5-dca and µ1,3-azide bridges, respectively to form 1D coordination polymers. The magnetic measurements showed the presence of antiferromagnetic interactions between Mn∙∙∙Mn cores in both of the obtained 1D coordination polymers, whereat the exchange interaction is an order of magnitude stronger in azido compared to dicyanamido bridged compound (–3.7 cm⁻¹ vs. –0.30 cm⁻¹).
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The aim: Thepaper wasaimedat thestudyof thebiomineralization processesofa permanentdental crown in thepostnatal period of histogenesis. Materials and methods: The study involved 30 culled puppies aged 30-40 days. To study the histogenesis of the germs of the permanent tooth from the cuticular epithelium in the postnatal period microscopic, electron microscopic, immunohistochemical methods of study have been used. Results: The studies show that in the postnatal period, the maturation of the germ of a permanent tooth starts with the synthesis of cells of the cuticular epithelium of the organic stroma, capable of subsequent mineralization. Differentiation of the proameloblasts, located on the surface of the dental papillary mesenchyma, at the early stages of histogenesis, is strongly associated with the appearance of a specific protein taftelin. Origination of secretory ameloblasts, which produce the protein enamelin, triggers the process of secondary biomineralization of the enamel. The terminal processes of the secretory ameloblasts produce the protein in the form of layers that overlap each other at a certain angle. Such layering of the structures of enamel and dentin contributes to the S-shaped maturation of the hard tooth tissues, strengthening them considerably. At the follicle stage, maturation of the dental crown, coated with cuticular epithelium, occurs. Invaginations of the cuticular epithelium form a characteristic topography of the dental crown, and enamel projections are further formed by the ameloblasts. Epitheliocytes of the inner layer of the enamel organ have desmosomal connections that allow the filtration of the salivary fluid at the stage of the enamel trophism. Conclusions: The findings of the study suggest that, normally, due to the cuticular epithelium, filtration of the salivary fluid occurs with protein deposition on it and subsequent infiltration of the calcium salts into the subjacent enamel.
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This review offers an overview of the influence of reactive species produced during exercise and their effect on exercise adaptation. Reactive species and free radicals are unstable molecules that oxidize other molecules in order to become stable. Although they play important roles in our body, they can also lead to oxidative stress impairing diverse cellular functions. During exercise, reactive species can be produced mainly, but not exclusively, by the following mechanisms: electron leak at the mitochondrial electron transport chain, ischemia/reperfusion and activation of endothelial xanthine oxidase, inflammatory response, and autooxidation of catecholamines. Chronic exercise also leads to the upregulation of the body's antioxidant defence mechanism, which helps minimize the oxidative stress that may occur after an acute bout of exercise. Recent studies show a beneficial role of the reactive species, produced during a bout of exercise, that lead to important training adaptations: angiogenesis, mitochondria biogenesis, and muscle hypertrophy. The adaptations occur depending on the mechanic, and consequently biochemical, stimulus within the muscle. This is a new area of study that promises important findings in the sphere of molecular and cellular mechanisms involved in the relationship between oxidative stress and exercise.
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Oxidative stress plays an important role in the development of microangiopathic complications in type 1 diabetes. We investigated polymorphic markers in genes encoding enzymes regulating production of reactive oxygen species in association with diabetic retinopathy or diabetic nephropathy. A total of 124 patients with type 1 diabetes were investigated in this case-control study. All subjects were matched for sex, age, and duration of diabetes. Genotyping was conducted using real-time PCR for p.Val16Ala polymorphism in the MnSOD gene and c.C-262T in the promoter region of the CAT gene. Multiplex PCR method was used for determination of GSTM1 and GSTT1 polymorphic deletions. Fluorescence-labeled PCR amplicons and fragment analysis was used for assessing the number of pentanucleotide (CCTTT)n repeats in inducible nitric oxide synthase. A positive association of MnSOD genotype Val/Val (odds ratio [OR] 2.49, 95% CI 1.00-6.16, P = 0.045) and GSTM1-1 genotype (2.63, 1.07-6.47, P = 0.031) with diabetic retinopathy but not with diabetic nephropathy was demonstrated. Additionally, the combination of the two genotypes conveyed an even higher risk (4.24, 1.37-13.40, P = 0.009). No other investigated genetic polymorphisms were associated with either diabetic retinopathy or diabetic nephropathy. Selected polymorphisms in genes encoding MnSOD and GSTM1 could be added to a panel of genetic markers for identification of individuals with type 1 diabetes at an increased risk for developing diabetic retinopathy.
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Exercise-induced oxidative stress is a state that primarily occurs in athletes involved in high-intensity sports when pro-oxidants overwhelm the antioxidant defense system to oxidize proteins, lipids, and nucleic acids. During exercise, oxidative stress is linked to muscle metabolism and muscle damage, because exercise increases free radical production. The T allele of the Ala16Val (rs4880 C/T) polymorphism in the mitochondrial superoxide dismutase 2 (SOD2) gene has been reported to reduce SOD2 efficiency against oxidative stress. In the present study we tested the hypothesis that the SOD2 TT genotype would be underrepresented in elite athletes involved in high-intensity sports and associated with increased values of muscle and liver damage biomarkers. The study involved 2664 Caucasian (2262 Russian and 402 Polish) athletes. SOD2 genotype and allele frequencies were compared to 917 controls. Muscle and liver damage markers [creatine kinase (CK), creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP)] were examined in serum from 1444 Russian athletes. The frequency of the SOD2 TT genotype (18.6%) was significantly lower in power/strength athletes (n = 524) compared to controls (25.0%, p = 0.0076) or athletes involved in low-intensity sports (n = 180; 33.9%, p < 0.0001). Furthermore, the SOD2 T allele was significantly associated with increased activity of CK (females: p = 0.0144) and creatinine level (females: p = 0.0276; males: p = 0.0135) in athletes. Our data show that the SOD2 TT genotype might be unfavorable for high-intensity athletic events.
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Reactive oxygen species (ROS) are generated as a consequence of metabolic reactions in the mitochondria of eukaryotic cells. This work describes the role of the manganese superoxide dismutase (MnSOD) as a biomarker of different human diseases and proposes a new therapeutic application for the prevention of cancer and its treatment. The paper also describes how a new form of human MnSOD was discovered, its initial application, and its clinical potentials. The MnSOD isolated from a human liposarcoma cell line (LSA) was able to kill cancer cells expressing estrogen receptors, but it did not have cytotoxic effects on normal cells. Together with its oncotoxic activity, the recombinant MnSOD (rMnSOD) exerts a radioprotective effect on normal cells irradiated with X-rays. The rMnSOD is characterized by the presence of a leader peptide, which allows the protein to enter cells: this unique property can be used in the radiodiagnosis of cancer or chemotherapy, conjugating radioactive substances or chemotherapic drugs to the leader peptide of the MnSOD. Compared to traditional chemotherapic agents, the drugs conjugated with the leader peptide of MnSOD can selectively reach and enter cancer cells, thus reducing the side effects of traditional treatments.
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Oxidative damage is one threat spermatozoa have to face during epididymal maturation and storage. However, it is clear that reactive oxygen species (ROS) are also central for sperm physiology in processes such as sperm maturation and capacitation. It is therefore essential that there exists around sperm cells a fine balance between ROS production and recycling. To do so, sperm cells and epididymal epithelial cells rely on common enzymatic ROS scavengers such as superoxide dismutase (SOD), glutathione peroxidases (GPX) and catalase (CAT) as well as more specific types such as indoleamine dioxygenase (IDO). Among the catalytic triad (SOD/GPX/CAT), the glutathione peroxidase protein family occupies a peculiar position, since several GPX have been found to be present on and around epididymal transiting sperm cells. Here, we will review our present knowledge regarding GPX expression, presence and putative role(s) within the epididymis and on spermatozoa. Taking into account our recent findings regarding the epididymal expression of indoleamine dioxygenase in mouse we will also discuss how we think this superoxide anion recycling enzyme completes the complex ROS generation/recycling balance in this organ.
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Introduction: We assessed the predictive value of electrophysiological tests as a marker of clinical disease onset and survival in superoxide-dismutase 1 (SOD1)(G93A) mice. Methods: We evaluated the accuracy of electrophysiological tests in differentiating transgenic versus wild-type mice. We made a correlation analysis of electrophysiological parameters and the onset of symptoms, survival, and number of spinal motoneurons. Results: Presymptomatic electrophysiological tests show great accuracy in differentiating transgenic versus wild-type mice, with the most sensitive parameter being the tibialis anterior compound muscle action potential (CMAP) amplitude. The CMAP amplitude at age 10 weeks correlated significantly with clinical disease onset and survival. Electrophysiological tests increased their survival prediction accuracy when evaluated at later stages of the disease and also predicted the amount of lumbar spinal motoneuron preservation. Conclusions: Electrophysiological tests predict clinical disease onset, survival, and spinal motoneuron preservation in SOD1(G93A) mice. This is a methodological improvement for preclinical studies.