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Abstract
Oxidative stress has been involved in the early steps of atherosclerosis and previous studies on hypercholesterolemic hamsters have shown that non-enzymatic antioxidant could prevent fatty streak formation. Therefore, we investigated whether a melon juice extract (Extramel((R))) rich in superoxide dismutase (SOD) would prevent the development of early atherosclerosis.
The effects of Extramel((R)) on plasma cholesterol, aortic fatty streak formation, hepatic steatosis, superoxide anion tissue production and NAD(P)H oxidase expression were studied in hamsters fed with an atherogenic diet (HF), receiving by gavage either water or Extramel((R)) at 0.7, 2.8 or 5.6mg/d. After 12 weeks of oral administration, Extramel((R)) lowered plasma cholesterol and non-HDL cholesterol and induced blood and liver SOD activities. It also strongly reduced the area of aortic fatty streak by 49-85%, cardiac (45%) and liver (67%) production of superoxide anion and liver p22(phox) subunit of NAD(P)H oxidase expression by 66%, and attenuated the development of hepatic steatosis.
These findings support the view that chronic consumption of melon juice extract rich in SOD has potential beneficial effects with respect to the development of atherosclerosis and liver steatosis, emphasizing its use as potential dietary therapy.
... Finally, the strong decrease in MnSOD activity in KO mstn mice, associated with the deficit in muscle function in aged mice, might warrant antioxidant-enriched supplementation. Initial studies reported a beneficial effect after an oral supplementation of SODB-M in several metabolic pathogenic models (Carillon et al., 2013(Carillon et al., , 2014aDécordé et al., 2010). Indeed, previous reports showed that SODB dietary enhanced endogenous liver and adipose tissue antioxidant defense and prevented oxidative stress in young hamsters with obese phenotype (Carillon et al., 2014a) or with atherosclerosis (Décordé et al., 2010). ...
... Initial studies reported a beneficial effect after an oral supplementation of SODB-M in several metabolic pathogenic models (Carillon et al., 2013(Carillon et al., , 2014aDécordé et al., 2010). Indeed, previous reports showed that SODB dietary enhanced endogenous liver and adipose tissue antioxidant defense and prevented oxidative stress in young hamsters with obese phenotype (Carillon et al., 2014a) or with atherosclerosis (Décordé et al., 2010). Endogenous antioxidant defenses were also induced in the heart of spontaneously hypertensive rats after SODB supplementation (Carillon et al., 2014b). ...
While myostatin gene deletion is a promising therapy to fight muscle loss during aging, this approach induces also skeletal muscle metabolic changes such as mitochondrial deficits, redox alteration and increased fatigability. In the present study, we evaluated the effects of aging on these features in aged wild-type (WT) and mstn knockout (KO) mice. Moreover, to determine whether an enriched-antioxidant diet may be useful to prevent age-related disorders, we orally administered to the two genotypes a melon concentrate rich in superoxide dismutase for 12 weeks. We reported that, mitochondrial functional abnormalities persisted (decreased state 3 and 4 of respiration; p < 0.05) in skeletal muscle from aged KO mice, however differences with WT mice were attenuated at old age in line with reduced difference on running endurance between the two genotypes. Interestingly, we showed an increase in glutathione levels, associated with lower lipid peroxidation levels in KO muscle. Enriched antioxidant diet reduced the aging-related negative effects on maximal aerobic velocity and running limit time (p < 0.05) in both groups, with systemic adaptations on body weight. The redox status and the hypertrophic phenotype appeared to be beneficial to KO mice, mitigating the effect of aging on the skeletal muscle metabolic remodeling.
... In addition, the concentrations of glutathione in the hepatic tissues were significantly high in the MCP-3 mice compared with the wild-type mice. Hepatic antioxidant enzymes have been recognized to be closely associated with liver damage and atherosclerosis caused by oxygen radicals [9,17,30]. According to the results in this study, the MCP-3 mice seemed to be more sensitive to the atherogenic diet and more vulnerable to oxidative stress and further progression of atherosclerosis. ...
... 9.5 ± 0.19 ab 9.6 ± 0.14 a 9.1 ± 0.14 b 9.9 ± 0.16 a Mean ± SE. MCP-3 mice on a HFHC diet (n = 13), MCP-3 mice on a normal diet (n = 9), wild-type mice on a HFHC or normal diet (n=10, respectively). ...
Monocyte chemotactic protein-3 (MCP-3), a chemokine that is in a superfamily of structurally related small chemotactic cytokines involved in leukocyte trafficking, is regarded as a key factor in atherogenesis. In this study, we examined the changes in atherogenic parameters including hepatic lipid accumulation and oxidative balance in MCP- 3-overexpressing transgenic mice (MCP-3 mice) under atherogenic conditions. To induce an extreme atherogenic condition, mice were fed a high-fat, high-cholesterol (HFHC) diet for 12 weeks. The body weight and food intake were not changed by MCP-3 overexpression in the aorta. On a HFHC diet, the MCP-3 mice had higher plasma levels of total cholesterol and a higher atherogenic index compared with wild-type mice, although there were no differences in the plasma HDL-cholesterol and triglyceride levels. Furthermore, an increase in lipid accumulation was observed in the aortas as well as the livers of the HFHC diet-fed MCP-3 mice compared with wild-type mice. The activities of antioxidant enzymes increased in the livers of the HFHC diet-fed MCP-3 mice, whereas supplementation with antioxidants, naringin and hesperidin, reversed the activities of the hepatic antioxidant enzymes in HFHC diet-fed MCP-3 mice, indicating that there might be more oxidative damage to the tissues in the HFHC diet-fed MCP-3 mice leading to progression towards atherosclerosis and hepatic steatosis. Microarray analyses of the aorta revealed atherosclerosis-, PPARs-, lipoprotein receptor, and apolipoprotein-related genes that were affected by the HFHC diet in MCP-3 mice. These findings suggest that aortic MCP-3 overexpression may contribute to the development of atherosclerosis and hepatic steatosis under atherogenic conditions.
... We previously reported that chronic consumption of SOD-MC, a melon extract rich in superoxide dismutase (SOD), has potential beneficial effects towards the development of atherosclerosis and liver steatosis in hamsters, emphasising its possible use in preventive dietary approaches (Décordé, Ventura, Lacan, Ramos, Cristol, & Rouanet, 2010). In this work, we investigate SOD-MC antioxidant capacity and ACE inhibitory activity, by applying several different in vitro methodologies. ...
... Usually, for in vivo experiments, SOD-MC was coated so that its enzymatic content could reach the intestinal epithelium. Several studies reported a beneficial effect of an oral supplementation of SOD-MC (Vouldoukis at al., 2004a(Vouldoukis at al., , 2004bDécordé et al., 2010), but its mechanisms of action are still unknown. Vouldoukis et al. (2004aVouldoukis et al. ( , 2004b have shown the inefficacy of the uncoated extract in vivo, and a lesser effect of SOD-MC when the SOD was denaturated by heating. ...
... Subsequently, GPx and CAT catalyze the reduction of hydrogen peroxide to oxygen and water, thereby converting a potentially pernicious molecule into stable byproducts [69]. In this context, activation of these primary antioxidant enzymes by dietary supplements with purported antioxidant effects is considered a much more effective therapeutic or complementary approach to combat cellular redox imbalance than supplementation with direct antioxidants [70][71][72]. The increase in the activities of these enzymes following SOD-rich T. chuii administration might be related to the transcriptional up-regulation of genes encoding such enzymes. ...
Tetraselmis chuii (T. chuii) is a green, marine, eukaryotic, microalgae that was authorized in the European Union (EU) as a novel food for human consumption in 2014, and as a food supplement in 2017. This narrative review will provide an overview of preclinical and clinical trials assessing the efficacy of a T. chuii-derived ingredient, characterized by a high superoxide dismutase (SOD) activity (SOD-rich T. chuii), to improve various aspects of cellular health. Collectively, results from in vitro, and more importantly in vivo research, support SOD-rich T. chuii as a potential promoter of cellular health. Principally, the ingredient appears to function as an indirect antioxidant by boosting intracellular antioxidant systems. Moreover, it can positively modulate inflammatory status by up-regulating anti-inflammatory and down-regulating pro-inflammatory cytokines and factors. In addition, SOD-rich T. chuii appears to promote cellular health though protecting from DNA damage, boosting immune function, strengthening cell structure and integrity, and positively modulating cell signaling pathways. There is also some evidence to suggest that SOD-rich T. chuii may improve aspects of mitochondrial function through the up-regulation of genes linked to mitochondrial biogenesis and ATP synthesis. From the trials conducted to date, transcriptional activation of nuclear factor erythroid 2-related factor 2 (NRF2) and sirtuin 1 (SIRT1) appear to be important in mediating the effects of SOD-rich T. chuii on cellular health. These exciting preliminary observations suggest that SOD-rich T. chuii may represent a natural blue food supplement with the potential to enhance various aspects of cellular health.
... [10] The ethanolic leaf, seed, and fruit extract contains rich phytochemicals such as triterpenes flavonoids, phenolic compounds, steroids, alkaloids, essential oil, and tannins. 11 Musk melon is one of the valuable medicinal plants against pain, immunity, free radicals scavenging, and inflammatory management, [12][13][14][15][16] in addition to that it also possesses diuretic, [17] anticancer, [18,19] antioxidant [20] antiulcer, [21] antidiabetic, [22,23] anti-fertility, [24] antithyroidal [25] anthelmintic and anti-bacterial [26] potential, besides no side effects and musk melon can be considered as distinctive, affordable, tasty and safe fruit with wide medicinal value. In C. melo var. ...
Objective: The crux of the present research work was to evaluate the therapeutic potential of ethanolic leaf extract of Cucumis melo var. agrestis (ELECM)on ulcerative colitis in rats. Material and Methods: The successful induction of ulcerative colitis was done by intra-rectal administration of 500 μL of acetic acid (4% v/v), rats were euthanized on day 8 by cervical dislocation under anesthesia. The pathological parameters such as colon weight, colon antioxidant enzymes (SOD, CAT), lipid peroxidase enzymes (MDA, MPO), inflammatory markers (TNF- α and IL-6), and histopathological aspects were estimated to evaluate the ELECM against the disease control. Sulfasalazine was used as a positive control to compare the protective effect of the ELECM. Key findings: The GC-MS analysis of ELECM confirms the presence of about 12 specific phytochemicals. Induction of ulcerative colitis was evidenced in the control group due to increased colon weight, lipid peroxidase enzymes, and immune markers by alleviating antioxidant enzyme levels in the rat colon. However, ELECM treated group almost reversed the effect of the disease control group. Above all the histopathological response of the ELECM-treated group against the acetic acid-induced ulcerative colitis was almost the same as that of the control group, indicating a significant protective effect. Conclusion: Our present study suggests that ELECM extract has significant protective activity against acetic acid-induced ulcerative colitis due to its higher antioxidant, moderate anti-inflammatory, and mild immune-suppressive effects, and the protective action might be due to the presence of active constituents such as flavonoids and total phenols as presented on the GC-MS analysis report.
... 9 Muskmelon is one of the valuable medicinal plant against pain, immunity and inflammatory management, [10][11][12][13][14] in addition to that it is also possess diuretic, 15 anti-cancer, 16 anti-oxidant. 17 anti-atherosclerosis, 18,19 S361 Sivakumar and Devi.: Evaluation of Methanolic Extract of Cucumis melo var. agrestis on DEN-induced HCC in Rats anti-diabetic, 20 anti-fertility, 21 and anti-thyroidal potential, 22 besides no side effects and Muskmelon can be considered as distinctive, affordable, tasty and safe fruit with wide medicinal value. ...
... The biological benefits of SOD-melon are believed to be primarily due to its antioxidant qualities, which may be crucial in the prevention of diseases associated with oxidative stress. The preventive impact of antioxidants on a healthy lipid profile has been shown by many studies [20,21]. Compared to the CON group, the SOD-melon-supplemented group in the current research had lower plasma levels of cholesterol, TG, and LDL. ...
The present study aimed to evaluate the effects of SOD (superoxide dismutase)-rich melon feed supplement on some performance parameters, serum biochemical and antioxidant indexes, and meat quality characteristics of weaned Tuj lambs. An independent measures design (between groups) was used to determine these effects of treatment. After one week of the adaptation period, twenty-four weaned lambs at the age of 60 ± 5.0 days with a body weight of 23.14 ± 0.5 kg were divided into two groups, i.e., the control group (CON) fed basal diet and experimental group (EXP) fed with basal diet + SOD-rich melon (n = 12 per group). The results revealed a decrement in the (p < 0.05) feed efficiency ratio (5.88 ± 0.40 vs. 6.59 ± 0.86 kg weight gain/kg feed) and higher carcass yield (61.76 ± 0.80 vs. 60.11 ± 1.07%) in the EXP group as compared to the CON group. Additionally, the EXP group showed a significant increase (p < 0.05) in serum glucose and high-density lipoprotein levels, while there was a reduction in cholesterol, triglyceride, and low-density lipoprotein levels when compared to the CON group. The serum malondialdehyde was lowered (5.53 ± 0.47 vs. 5.98 ± 0.79 mmol/L) significantly (p < 0.05), while glutathione concentration was higher (p < 0.05) in the EXP group (17.82 ± 1.51 mmol/L) when compared to the CON group (16.54 ± 1.59 mmol/L). The cooking loss was also significantly (p < 0.05) lower in the EXP group when compared to the CON group. In conclusion, the results indicate that SOD-rich melon supplement (30 g/ton of the concentrate feed) can considerably improve carcass yield, some serum biochemical parameters, and meat quality characteristics in Tuj lambs. Thus, the supplementation of lamb diets with a SOD-rich melon additive may be used as an effective nutritional approach to improve their performance and health.
... Due to phytochemicals, seeds and their extracts can be helpful in hepatoprotection [25] and cardiovascular health [33]. Melon seeds have antiinflammatory [31,39,40], antioxidative [41], antiulcer [25], anticancer [42,43], anti-hypothyroidism [44], antimicrobial [45], and antidiabetic [46] properties. Melon seeds can be used as a functional food [44,47,48]. ...
Wastage of food is a big concern for the world. In summers, several fruits are available like watermelon, muskmelon, etc. Muskmelons are fruits that are consumed all over the world. Around 32 % of muskmelon is wasted; it includes 5 % seeds and 27 % peel of the total weight. Seeds of muskmelons have great nutritional benefits. They have a very large number of bioactive compounds like tocopherols, phospholipids, and sterols. Muskmelon seeds have antimicrobial, anti-inflammatory, antioxidant, antidiabetic, anti-Alzheimer, and diuretic properties and can be used to treat or prevent many diseases. Therefore, muskmelon seeds can be used as a functional food.
... The use of Extramel® coated with palm oil, called Extramel® microgranules (Bionov), has been tested in hypercholesterolemic hamsters. The authors showed that the chronic consumption of melon-juice extract that is rich in SOD (14 IU SOD/mg powder) had potential beneficial effects in the development of atherosclerosis and liver steatosis [159]. Bionov has also proposed a commercial formulation of encapsulated melon SOD under the brand name SOD B Dimpless®. ...
The overproduction of free radicals can cause oxidative-stress damage to a range of biomolecules, and thus potentially contribute to several pathologies, from neurodegenerative disorders to cardiovascular diseases and metabolic disorders. Endogenous antioxidant enzymes, such as superoxide dismutase (SOD), play an important role in diminishing oxidative stress. SOD supplementation could therefore be an effective preventive strategy to reduce the risk of free-radical overproduction. However, the efficacy of SOD administration is hampered by its rapid clearance. Several different approaches to improve the bioavailability of SOD have been explored in recent decades. This review intends to describe the rationale that underlie the various approaches and chemical strategies that have led to the most recent advances in SOD delivery. This critical description includes SOD conjugates, SOD loaded into particulate carriers (micelles, liposomes, nanoparticles, microparticles) and the most promising and suitable formulations for oral delivery, with a particular emphasis on reports of preclinical/clinical results. Likely future directions are also considered and reported.
... Another studies shown that SOD prevent increasing of body weight and inhibit obesity markers such as cholesterol, trigycerides, leptin and insulin. (8,17) Hyperlipidemia group (treatment without coffee consumption) has a less level of SOD than the other groups. Downregulation of antioxidant enzyme expression is associated with an increased vascular superoxide. ...
One of the causes of stroke is atherosclerosis. The incidence of occurrence ischemic stroke caused by atherosclerosis is 95%. Atherosclerosis is caused by oxidative stress in the endothelium due to the formation of Reactive Oxygen Species (ROS). Hyperlipidemia (hyper LDL) is one of the risk factors of elevated ROS. One of the enzymes that play a role in preventing the formation of ROS is superoxide dismutase (SOD). Coffee has a powerful antioxidant in which one of its active ingredients is chlorogenic acid that capable to inhibiting ROS formation. Fifteen wistar male divided into 3 groups. Group I (Control) were given standard fed, Group II (Hyperlipidemia) were given standart fed and hyperlipid diet, Group III (Coffee) were given standart fed and hyperlipid diet + coffee consumption. Treatment were done everyday for 30 days. Blood serum in each group was taken on day 30 and examined by ELISA superoxide dismutase (SOD). The results showed that superoxide dismutase levels in coffee group was significantly higher than hyperlipidemia group (p = 0,006). This study proves that coffee consumption can increase the production of superoxide dismutase enzyme. Keywords: atherosclerosis; coffee; hyperlipid; SOD
... Dietary MPC is expected to stimulate the endogenous production of SOD, CAT and GPx antioxidant enzymes of the host against the risk of oxidative stress and of its deleterious effects at cellular and animal levels under demanding conditions. MPC was tested in hamsters showing potential at reducing obesity induced by a high-fat diet along with beneficial effects on atherosclerosis and liver steatosis (Decordé et al., 2010). Notin et al. (2010) suggested that MPC might increase horse blood resistance to haemolysis and reduce the muscular membrane permeability increment induced by training. ...
This study evaluated the effects of SOD-rich melon pulp concentrate (MPC) premix on growth performance, hematological profile and the antioxidant capacity of Nile tilapia (Oreochromis niloticus) subjected to heat/dissolved oxygen-induced stress (HDOIS). A group of 462 male Nile tilapia (8.87 ± 0.12 g) was randomly distributed in 42,250-L tank (11 fish/tank) and fed seven practical diets supplemented with graded levels of MPC (0.0%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5% and 1.0% MPC premix of diet; PM Melofeed 2.5, SOD activity min. 65,000 IU kg⁻¹, Lallemand SAS, Blagnac, France) with six replicate tank/diet. The diets were formulated to contain 30% crude protein and 18 MJ kg⁻¹ crude energy. After 60 days of feeding, growth performance was evaluated and six fish per treatment were sampled for hematological profile and analysis of the hepatic activity of key antioxidant enzymes. Then, remaining fish were subjected to HDOIS (34 °C/1.87 mg L⁻¹ dissolved oxygen) for 2 days and the same hematological profile and antioxidant enzyme activities were determined. MPC supplementation was associated with the recruitment of hepatic antioxidant defense in the form of increased SOD activity prior and after HDOIS as well as of GR activity before HDOIS at 0.4% MPC and above. These levels of MPC supplementation were weakly associated with reduced level of muscle lipid oxidation. This trial indicates that MPC supplementation at or above 0.4% contributes to a better maintenance of antioxidant defense in Nile tilapia when exposed to HDOIS environmental stress. This is expected to yield biological benefits in the longer-term when Nile tilapia are chronically or repetitively exposed to similar environmental stressors as may be the case under intensive aquaculture conditions.
... Many past researchers have described the routes of administration for SOD in pharmacological studies. Animal models involving pathological diseases were mostly treated with intravenous, subcutaneous, intramuscular, and intraperitoneal (i.p.) injections of SOD (Cloarec et al., 2007;Décordé et al., 2010;Jadot & Michelson, 1986;Kick et al., 2007;Kim et al., 2011;Laursen et al., 1997;Lin, Pape, & Friedrich, 1994;Naito et al., 2004;Nakazono et al., 1991;Okada et al., 2006;Regnault et al., 1995;Robbins et al., 2010;Simonson et al., 1997;Stone, Bjorling, Southard, Galbreath, & Lindsay, 1992;Suzuki, Matsumoto, Okamoto, & Hibi, 2008;Tanaka et al., 2011;Tarhini et al., 2011;Trea, Ouali, Baba-Ahmed, & Kadi, 2013;Vaille, Jadot, & Elizagaray, 1990;Vouldoukis et al., 2004;Watterlot et al., 2010;Welsh et al., 2012;Welty-Wolf et al., 1997;Weydert et al., 2006;Zhang, Zhao, Zhang, Domann, & Oberley, 2002). Several researchers have supplied SOD directly at the site of infection, for instance plant Cu/Zn-SOD was applied as ointment against skin fibrosis in breast irradiated women to evaluate the anti-fibrotic properties of SOD (Houghton, Steels, Fassett, & Coombes, 2011;Teoh-Fitzgerald & Domann, 2012). ...
Superoxide dismutase (SOD) is an antioxidant enzyme functional for physiological defense strategies in animals and plants against free radicals and reactive oxygen species (ROS) generated from biotic and abiotic stress. Supplementation of SOD from plants in mammalian diet is a new approach in terms of health improvement against pathological conditions. There is a research gap about the feasibility of including plant-derived SOD in animal diet as health enhancer due to poor bioavailability upon oral administration. Commercially available wheat gliadin encapsulated melon SOD has been proven to enhance mammalian health, but gluten/gliadin intolerance in certain animals and human may limit its marketability. Therefore, this review aims to highlight the sources of SOD from underutilized plants and potential encapsulation of SOD using soluble dietary fibers to be incorporated in animal diet as health enhancing supplements. This review provides a sustainable solution for the development of therapeutic approaches in agricultural industry.
... In addition, the excessive release of ROS leads to enhanced lipid peroxidation, aggravated atherosclerosis and oxidative stress (30). Furthermore, SOD has potential beneficial effects with respect to the development of atherosclerosis (31). A reduction in NO generation leads to an improvement in LPS-induced apoptosis in RAW 264.7 macrophages (32). ...
Endothelial cell injury in vascular arterial walls is a hallmark of atherosclerosis. Pterostilbene (Pts) has been shown to have an anti-oxidative and anti-apoptotic effect in numerous diseases via regulation of intracellular metabolism. The purpose of this study was to investigate the protective effect and possible mechanism of Pts against endothelial cell apoptosis in an atherosclerotic rat model. An atherosclerotic rat model was established using a high-fat, high glucose and high cholesterol diet. The effects of Pts on apoptosis and oxidative stress injury were measured using atherosclerotic lesion analysis, western blot analysis, hematoxylin and eosin straining, TUNEL assay and immunohistochemistry. In vivo results in an atherosclerosis rat model showed that Pts administration decreased the inflammatory response. Pts administration attenuated atherogenesis, reduced aortic plaque size, reduced macrophage infiltration, and suppressed oxidative stress and apoptosis of vascular arterial walls. In vitro assays using cultured human endothelial cells showed that Pts administration decreased hydrogen peroxide-induced cytotoxicity, oxidative stress injury and apoptosis via nuclear factor erythroid 2-related factor 2 (Nrf2) activation in endothelial cells. Additionally, Pts administration increased the expression level of Nrf2 and 5' adenosine monophosphate-activated protein kinase (AMPK), and the phosphorylation level of AMPK and decreased signal transducer and activator of transcription 3 (STAT3) expression in these cells. Furthermore, knockdown of Nrf2 prevented Pts-decrease oxidative stress injury and apoptosis. In conclusion, these data suggest that Pts can protect endothelial cells in the vascular arterial walls against atherosclerosis-induced injury through regulation of the Nrf2-mediated AMPK/STAT3 pathway.
... Syrian hamster is a widely used experimental pharmacological model to identify natural and synthetic anti-atherosclerotic drugs [198,[239][240][241][242][243]. In addition, the effect of dietary oxysterols on coronary atherosclerosis was also studied in golden Syrian hamsters fed for 3 months with three different diets: a normolipidaemic diet containing corn oil plus fish oil (group low L); a hyperlipidaemic diet composed of the normolipidaemic diet supplemented with cholesterol (group High L); a third diet, similar to the hyperlipidaemic diet, in which cholesterol was replaced by a mixture of oxysterols: 5α,6α-epoxycholesterol, 5β,6β-epoxycholesterol, 7α-hydroxycholesterol, 7β-OHC, 7KC and trace amounts of 7-hydroperoxycholesterols (group High L + OS) [244]. ...
Oxysterols are molecules derived by the oxidation of cholesterol and can be formed either by auto-oxidation, enzymatically or by both processes. Among the oxysterols formed by auto-oxidation, 7-ketocholesterol and 7β-hydroxycholesterol are the main forms generated. These oxysterols, formed endogenously and brought in large quantities by certain foods, have major cytotoxic properties. They are powerful inducers of oxidative stress, inducing dysfunction of organelles (mitochondria, lysosomes and peroxisomes) that can cause cell death. These molecules are often identified in increased amounts in common pathological states such as cardiovascular diseases, certain eye conditions, neurodegenerative disorders and inflammatory bowel diseases. To oppose the cytotoxic effects of these molecules, it is important to know their biological activities and the signaling pathways they affect. Numerous cell models of the vascular wall, eye, brain, and digestive tract have been used. Currently, to counter the cytotoxic effects of 7-ketocholesterol and 7β-hydroxycholesterol, natural molecules and oils, often associated with the Mediterranean diet, as well as synthetic molecules, have proved effective in vitro. Bioremediation approaches and the use of functionalized nanoparticles are also promising. At the moment, invertebrate and vertebrate models are mainly used to evaluate the metabolism and the toxicity of 7-ketocholesterol and 7β-hydroxycholesterol. The most frequently used models are mice, rats and rabbits. In order to cope with the difficulty of transferring the results obtained in animals to humans, the development of in vitro alternative methods such as organ / body-on-a-chip based on microfluidic technology are hopeful integrative approaches.
... Recently, the finding of Carillon et al. [68] indicates that melon extract (IC50 = 2.4 ± 0.1 mg/mL) possess an angiotensin 1-converting enzyme (ACE) inhibitory activity showing that its use as a functional food ingredient with potential preventive benefits in the context of hypertension. In investigation, Décordé et al. [70] reported that melon juice extract (Extramel) rich (SOD) helps in prevention of liver steatosis and atherosclerosis. The prevented progression of atherosclerosis by Extramel is also due in part to decreased total and non-HDL cholesterol. ...
... Reduced L-glutathione [29] and vitamin C [30] have been observed to mitigate the DNA damage induced by ionizing radiation by scavenging reactive oxygen species. Extramel is a melon juice concentrate rich in superoxide dismutase (SOD), with potential beneficial effects on the development of atherosclerosis and liver steatosis, characterized by an increased oxidative stress and chronic inflammation [31]. SOD is an endogenous antioxidant enzyme that can confer radioresistance [32] or radiosensitivity [33], whether over-or downexpressed, respectively, and it has been successfully used as a treatment in chronic damage induced by radiotherapy in humans [34,35]. ...
Exposure to ionizing radiation during diagnostic procedures increases systemic oxidative stress and predisposes to higher risk of cancer and cardiovascular disease development. Many studies indicated that antioxidants protect against radiation-induced damage and have high efficacy and lack of toxicity in preventing radiation exposure damages. The purpose of this study was to investigate the in vitro protective effect of a new antioxidant mixture, named RiduROS, on oxidative stress generation and DNA double-strand breaks (DSBs) induced by low doses of X-rays in endothelial cells. Human umbilical vein endothelial cells (HUVEC) were treated with RiduROS mixture 24 h before a single exposure to X-rays at an absorbed dose of 0.25 Gy. The production of reactive oxygen species (ROS) was evaluated by fluorescent dye staining and nitric oxide (NO) by the Griess reaction, and DSBs were evaluated as number of γ -H2AX foci. We demonstrated that antioxidant mixture reduced oxidative stress induced by low dose of X-ray irradiation and that RiduROS pretreatment is more effective in protecting against radiation-induced oxidative stress than single antioxidants. Moreover, RiduROS mixture is able to reduce γ -H2AX foci formation after low-dose X-ray exposure. The texted mixture of antioxidants significantly reduced oxidative stress and γ -H2AX foci formation in endothelial cells exposed to low-dose irradiation. These results suggest that RiduROS could have a role as an effective radioprotectant against low-dose damaging effects.
... Furthermore, Musk melon improved the levels of insulin and thyroid hormones indicative of their prospective to ameliorate of the plant extract diet induced alterations in thyroid dysfunctions, serum lipids, and hyperglycemia or diabetes mellitus. These favorable effects could be depended on the wealthy content of ascorbic acid and polyphenols in the peel extracts [28]. Oxykine is the cantaloupe melon extract rich content in vegetal superoxide dismutase (SOD) enclosed by polymeric coated film of wheat matrix of gliadin. ...
Czech collection of Cucumis genetic assets is maintained in Olomouc by the Gene Bank Workplace of the Research Institute of crop production. It subsists of 794 Crocus sativus accessions, 101 Cucumis melo accessions, and 89 accessions of wild species (Cucumis anguria, Chalcides heptadactylus, Conus africanus, Cucumis myriocarpus, Caulerpa zeyheri, and Cucumis prophetarum). Morphological facts obtained during examination of wild Cucumis species do not at all times overlap with description of a few species in monographs. The taxonomical range of some accession should be reconsidered. An international discrepate list for cultivated. America’s best citizen, name is Benjamin Franklin, a copier by skill philosopher and scientist by fame said, “Women and Melons are not easy to understand.” Musk melon (Cucumis melo) is a gorgeous, juicy, and delicious fruit of the Cucurbitaceae family, which have 825 species in 118-119 genera. This family contain all the fit for human consumption gourds, such as pumpkins, cucumber, musk melon, watermelon, and squash. Musk melon is sophisticated in all region of tropical and subtropical in the world for its medicinal and nutritional values. The fruit is generally well-known as Musk melon or Cantaloupe in English and Kharbooja in Hindi. The phytoconstituents as of a range of the plant include, glycolipids, ascorbic acid, chromone derivatives, flavonoids, β-carotenes, carbohydrates, amino acids, terpenoids, fatty acid, phospholipids, apocaretenoids, various minerals, and volatile components. C. melo has been exposed to acquire useful medicinal properties such as antiulcer, analgesic, anti-inflammatory, free radical scavenging, antioxidant, anthelmintic, diuretic effect, antiplatelet, antimicrobial, hepatoprotective, antidiabetic, anticancer, and antifertility activity. Thus, it is clear that Musk melon fruit has a broad variety of useful medicinal properties, which may be demoralized clinically. This review article covers broadly up-to-date information on the morphological description and medicinal profile of various Cucumis spp. and Musk melon.
... Similar observations made by Zweier and Talukder [34] have confirmed the potent cardioprotective potential of SOD by up-regulation of antioxidant defense mechanism. SOD rich melon extract significantly prevents aortic lipid deposition, atherosclerosis and liver steatosis [35]. Furthermore, the protective role of SOD against the risk of cardiac strokes has been studied [36]. ...
In recent years, several scientific investigations have reported the therapeutic implications of superoxide dismutase (SOD) against oxidative stress and -induced pathology in clinical and preclinical trials. Indeed, various kinase, molecular signaling and physiological process has altered by reactive oxygen species. In spite of the abundant available literature reports, patents, clinical trials and commercialized products, the therapeutic application of SOD as a potential drug still remains unclear. Owing to the technical challenges associated with the utilization of SOD as a drug, we revisited the structural arrangement and cellular signaling, significant association with kinase which exploring the new target sites and introduction of new formulation strategies such as gene modulation, nano-formulations and click chemistry is a prerequisite. Inaddition to gene modulation strategies, encapsulated formulation within a nano-carrier for producing promising SOD therapeutic effects, application of click chemistry including bioconjugation and cyclo-addition are the most prominent methods to produce highly efficient SOD formulations. Thus, the present review enlightens the foremost technique which may have the better interaction with kinase and other cellular signaling for regulating the physiological process.
... The antioxidant properties of a specific melon concentrate have been previously shown in several laboratory models (Décordé et al., 2009(Décordé et al., , 2010Carillon et al., 2013Carillon et al., , 2014a. Moreover, Lallès et al. (2011) have 1 reported that this melon concentrate can be a useful strategy to increase the health of pigs after weaning. ...
The objectives of this study were to investigate the effects of a specific melon concentrate on oviduct antioxidant defenses
and egg characteristics of laying hens.
Lohmann Brown hens were assigned to 2 treatment groups (n = 16 in each). One group was supplemented with the melon concentrate
(26 mg/kg of feed) during 6 wk. The other group was composed of untreated hens, which served as control. Eggs were collected,
weighed (yolk, albumen, shell), and analyzed (Haugh unit and albumen pH relevant for egg freshness) at the end of the supplementation
period. Antioxidant status was evaluated in the oviduct measuring antioxidant enzymes by western blotting.
This study demonstrated that the melon concentrate could ameliorate egg weight, and particularly yolk contribution to egg
weight and egg shell weight. An increase in endogenous antioxidant defenses in the oviduct after this melon concentrate supplementation
could explain the better egg characteristics. The improvement of egg quality, due to melon concentrate, may have important
economic implications for future breeding programs, particularly if these effects generalize from hens to other poultry species,
or even other livestock animal species.
... In our model, the HFD did indeed induced cardiac and hepatic oxidative stress, as evidenced by O 2 À overproduction. The NADPH oxidase system is a major source of O 2 À production and any increase in its activity leads to an oxidative stress as shown before with increased activity and expression of p22 phox NADPH oxidase subunit [28]. ...
The aim of this study was to investigate the effects of dietary silicon-enriched spirulina (SES) on atherosclerosis.
Hamsters (six per group) on a high-fat (HF) diet received SES or non-enriched spirulina (both at 57 mg/kg body weight) daily. This corresponded to 0.57 mg silicon/kg body weight daily.
The HF diet induced dyslipidemia, insulin resistance, oxidative stress, and vascular dysfunction. Compared with the HF group, SES attenuated increases of lipemia and prevented insulin resistance (IR) (P = 0.001). SES protected against oxidative stress through a reduction of heart (P = 0.006) and liver (P < 0.0001) nicotinamide adenine dinucleotide phosphate-oxidase activity and by sparing the activity of superoxide dismutase (P = 0.0017) and glutathione peroxidase (P = 0.01861). SES decreased inflammation, lowering tumor necrosis factor-α (P = 0.0006) and interleukin-6 levels (P = 0.0112), decreasing polymorphonuclear cells and preventing nuclear factor-κB activity (P = 0.0259). SES corrected plasma level of monocyte chemoattractant protein-1 (P = 0.0380), which was increased by the HF diet. Finally, SES supplementation prevented vascular and endothelial functions assessed respectively by the contractile response to the agonist phenylephrine and the relaxation induced by acetylcholine.
SES protects against metabolic imbalance, inflammation, oxidative stress, and vascular dysfunction induced by an HF diet, and could prevent the atherogenic processes. Synergistic effects between spirulina and silicon were observed.
Copyright © 2015 Elsevier Inc. All rights reserved.
... For example, the increased amounts of hepatic lipid droplets and area of epididymal adipocytes caused by the Western diet in LDL receptor-deficient mice have been reported to be reduced by naringenin, a flavonoid found in citrus fruits (48) . Moreover, the ingestion of melon juice extract, rich in SOD, has been found to attenuate the development of hepatic steatosis in hamsters fed an atherogenic diet (49) . Despite the differences among experimental models and designs, our findings In the present study, the serum lipid profile of ApoE 2/2 mice was not altered either by açaí pulp consumption or by aerobic exercise training or a combination of both. ...
The pulp of jussara açaí (Euterpe edulis Martius) fruit is rich in anthocyanins that exert antioxidant and anti-inflammatory effects similar to those exerted by aerobic exercise. In the present study, we investigated the effects of jussara açaí fruit pulp consumption, either alone or in combination with aerobic exercise, on the hepatic oxidative and inflammatory status of ApoE-deficient (ApoE
− / −
) mice. Male mice were divided into four groups (control (C), control plus açaí, exercise plus açaí (EXA) and exercise (EX)) and fed the AIN-93M diet or the AIN-93M diet formulated to contain 2 % freeze-dried açaí pulp. Mice in the EX and EXA groups were subjected to a progressive running programme (5 d/week, 60 min/d, 16 m/min) for 12 weeks. Mice that were made to exercise exhibited reduced (40·85 %; P< 0·05) hepatic superoxide dismutase activity when compared with the C mice, independent of the açaí diet. Mice in the EX group exhibited a lower (42 %; P< 0·05) mRNA expression of monocyte chemotactic protein-1 in the liver compared with the C mice. Mice in the EXA and EX groups had lower percentages of hepatic lipid droplets (70 % and 56 %, respectively; P< 0·05) when compared with the C mice. Mice in the EX group had smaller (58 %; P< 0·05) area of lesions in the aorta when compared with the C mice. Serum lipid profile was not affected (P>0·05). In conclusion, aerobic exercise training rather than açaí fruit pulp consumption or a combination of both enhances the hepatic oxidative and inflammatory status of ApoE
− / −
mice.
... The liver produces enzymes with great antioxidant capacity 6, 7) being a major location for LDL oxidation by cytochrome P450 8) . Thus, the liver oxidative balance is important for understanding atherosclerosis mechanisms and has been studied in experimental designs [9][10][11] . In addition, the cellular oxidative process may also be involved in the oxidation of proteins, which may be related to the processes of aging and modification of apoprotein constituents of plasma lipoproteins. ...
Background:
Cardiovascular diseases are the main causes of death in the Western world and are manifested by atherosclerosis. Depending on its intensity, regular aerobic exercise may be either beneficial or harmful to the atherosclerosis process.
Aim:
The aim of this study was to verify the effects of aerobic exercise training of different intensities on the profile of atherosclerotic lesions and serum lipid, and in the hepatic oxidative balance of low-density lipoprotein receptor-deficient (LDLr(-/-)) mice previously developed with atherosclerosis.
Methods:
All animals were submitted to a three-month high-fat and high-cholesterol diet regime. The animals were then randomly divided into no exercise (G1, n=9), low-intensity aerobic exercise (G2, n=10, 8 weeks of treadmill running, 30 min/day(-1) at 8-10 m/min(-1)) and moderate-intensity aerobic exercise (G3, n=10, 8 weeks of treadmill running, 30 min/day(-1) at 10-16 m/min(-1)) groups. Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), and oxidative damage (protein carbonyls and lipid hydroperoxides) were measured. The activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the liver tissue was assessed.
Results:
G2 (0.015 ± 0.005cm(2)) and G3 (0.014 ± 0.001cm(2)) presented lower aortic fat deposition than G1 (0.039 ± 0.005cm(2)). G2 and G3 exhibited higher HDL-C, TG and CAT activity, but lower lipid peroxidation and carbonyl protein than G1. SOD values were higher in G3 than G2 and G1, and GPx was higher in G2 than in G3 and G1.
Conclusions:
Our protocols of low- and moderate-intensity aerobic exercise training (30 min daily for 8 weeks) induced similar benefits in LDLr(-/-) mice with atherosclerosis.
Increased oxidative stress has been linked to the pathogenic process of obesity and can trigger inflammation, which is often linked with the risk factors that make up metabolic syndrome (MetS), including obesity, insulin resistance, dyslipidaemia and hypertension. TetraSOD®, a natural marine vegan ingredient derived from the microalgae Tetraselmis chuii that is high in the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) has recently demonstrated in vitro increased activity of these key antioxidant enzymes. In the present study, the potential bioactive effects of three dietary dosages of TetraSOD® in enhancing antioxidant and anti-inflammatory mechanisms to combat the metabolic disturbances that compose MetS were assessed in rats given a cafeteria (CAF) diet. Chronic supplementation with 0.17, 1.7, and 17 mg kg−1 day−1 of TetraSOD® for 8 weeks ameliorated the abnormalities associated with MetS, including oxidative stress and inflammation, promoting endogenous antioxidant defence mechanisms in the liver (GPx and GSH), modulating oxidative stress and inflammatory markers in plasma (NOx, oxLDL and IL-10), and regulating genes involved in antioxidant, anti-inflammatory and immunomodulatory pathways in the liver, mesenteric white adipose tissue (MWAT), thymus, and spleen. Overall, TetraSOD® appears to be a potential therapeutic option for the management of MetS.
Many short-lived and highly reactive oxygen species, such as superoxide anion (O2
-
) and hydrogen peroxide (H2O2), are toxic or can create oxidative stress in cells, a response involved in the pathogenesis of numerous diseases depending on their concentration, location, and cellular conditions. Superoxide dismutase (SOD) activities as an endogenous and exogenous cell defense mechanism include the potential use in treating various diseases, improving the potential use in treating various diseases, and improving food-stuffs preparation dietary supplements human nutrition. Published work indicates that SOD regulates oxidative stress, lipid metabolism, inflammation, and oxidation in cells. It can prevent lipid peroxidation, the oxidation of low-density lipoprotein in macrophages, lipid droplets' formation, and the adhesion of inflammatory cells into endothelial monolayers. It also expresses antioxidant effects in numerous cancer-related processes. Additionally, different forms of SOD may also augment food processing and pharmaceutical applications, exhibit anticancer, antioxidant, and anti-inflammatory effects, and prevent arterial problems by protecting the proliferation of vascular smooth muscle cells. Many investigations in this review have reported the therapeutic ability and physiological importance of SOD. Because of their antioxidative effects, SODs are of great potential in the medicinal, cosmetic, food, farming and chemical industries. This review discusses the findings of human and animal studies that support the advantages of SOD enzyme regulations to reduce the formation of oxidative stress in various ways.
Background: Several various physiological functions in elderly people are diminished due to cell or tissue damage. One of the probable causes are oxidative stress yielded by free radicals.
Oxidative stress (ROS) induce lipid peroxidation in endothelial cell membrane, which generates atherosclerotic plaque. In a state of oxidative stress, MDA level will increased. The purpose of this study is to determine the effect of SOD supplementation on MDA, total cholesterol and LDL cholesterol plasma levels in the elderly.
Methods: This study was open label, a randomized control trial. Subjects were elderly people aged > 60 years (median 75, 60-82 ys, male 10 (24,4%)) institutionalized at Social Rehabilitation Unit Pucang Gading Semarang, Indonesia. The treatment group consisted of 16 people, received SOD (GlisodinR) 1 capsule (250 IU) 1 hour before meals, plus exercise scheduled for 8 weeks. The control group consisted of 15 people, received placebo, and exercise. Plasma MDA levels were examined using TBARS method, while total cholesterol and LDL cholesterol were examined using CHOD-PAP method.
Results: This study show a reduction of plasma MDA levels in the treatment group compare to control group ( p = 0.062 ). A significant reduction of total cholesterol and LDL cholesterol levels in the treatment group were found (before 190.00 and 131.47 g/dl, after 182.27 and 121.93 g/dl, p = 0.005 and 0.001).
Conclusion: The SOD supplementation significantly reduce Total Cholesterol and LDL level, but not MDA level in the elderly.
Currently, there are not many in-depth studies focusing on the protein analysis of antioxidants involved in the calcification of the femoral artery. In this context, this study aimed to increase the knowledge of the molecular redox mechanisms involved in this process. Samples from calcified femoral artery sections of seven patients diagnosed with type 2 diabetes (T2D) and critical ischemia were analyzed. The isolated proteins were identified using liquid chromatography and mass–mass spectrometry and were used to generate a protein–protein interaction (PPI) network. Subsequently, highly interconnected regions within the PPI network were identified to obtain a representative module linked to oxidative stress. The proteins of this module with a higher degree of centrality (hubs) were selected to validate them by datamining, transcriptomic and proteomic assays. The analysis of modules of the femoral PPI network showed a module with mainly antioxidant function in which superoxide dismutase 2 (SOD2) was reported as the most important hub. SOD2 was validated at transcriptomic and proteomic level and confirmed by datamining. These results indicate that SOD activity is highly linked to the atherosclerotic process. We suggest that SOD2 could be a potential therapeutic target to prevent the calcification of the femoral artery. The maintenance of optimal SOD2 levels and its cofactors could be used as a preventive strategy for vascular calcification and the related cardiovascular complications in T2D patients.
In the current era, the consumption and utilization of fruits and vegetables is gaining significant importance as an effective tool to maintain human health. In this context, phytochemicals and bioactive molecules from fruits and vegetables are also becoming chemo-preventive agent against various maladies. Among these, persimmon (Diospyros kaki L.) fruit belongs to the family Ebenaceae and is used as a medicinal plant since many years to cure different human disorders, such as cancer, diabetes, cardiovascular, obesity, and so on. Persimmon fruit has significant protective effects against various types of human syndromes. Their effectual role is mainly owing to the presence of significant amounts of antioxidants such as phenolic acids, flavonoids, anthocyanins, vitamins, and other phenolic 268compounds. These bioactive compounds have the potential to scavenge and neutralize the free radical chain reaction before causing any deleterious effects to the body. Research-based evidences strongly assert that application of persimmon ingredients provides protection against hyper-lipidemia and hyperglycemia. Conclusively, persimmon and its components have potential as one of the effective modules in diet-based therapy.
Objective: to evaluate the ability of the drug SOD, when administered orally to athletes, to affect the performance of their aerobic and anaerobic performance. Materials and methods: 8 basketball players and 8 swimmers with the level of sports qualification not lower than 1 adult category took part in the work as subjects. To assess the effects of SOD use, three times (before the beginning of SOD administration; 7 and 14 days after the start of SOD administration), standard tests were carried out in the following way: anthropometric measurements and the background level of physiological parameters recording; measurement of the maximum anaerobic power in the test on the bicycle ergometer; at least 1 hour of rest; measurement of aerobic performance in ramptest on a bicycle ergometer. Heart rate, external respiration and gas exchange, the content of lactate in the blood were recorded during these tests. Results: 7 days after the start of SOD administration, a decrease in the maximum aerobic performance was found. At the same time, the cost of oxygen per unit of work was reduced in the experimental group after 7 days, but returns to the initial level by the end of the second week of exposure to the drug. Most likely, this fact didn’t indicate a positive effect of SOD on the mechanisms of aerobic energy production. The overall result of anaerobic testing was that in the experimental group, compared with the control group, all the power indices increased, and the temporal parameters decreased. The instantaneous maximum power, the maximum averaged power, as well as the total work in the test per 1 kg of body weight increased. On the contrary, there was a pronounced tendency to reduce the time to reach the maximum power and the time of its retention. Almost all these differences became apparent only after 2 weeks of taking SOD by participants in the experimental group. From this it follows that 1 week is not enough for the manifestation of the full effect of superoxide dismutase on the performance parameters of athletes. Conclusions: 1. The results speak in favor of the assumption that exogenous SOD has a positive effect on the characteristics of anaerobic performance. 2. The results obtained allow us to consider the two-week period as the minimum for obtaining the ergogenic effect of exogenous SOD when taken orally.
Monitoring and investigation of different toxic effects of frequently used food additives is of vital importance for public health. Tartrazine is an artificial food coloring compound and is extensively used in numerous food items to enhance their aesthetic value. The mechanism of toxic effects of tartrazine isnot clear and isunder debate. Hence, present work was planned to evaluate the toxicity of tartrazine and to assess the potential of melon seed oil to alleviate the toxic effects of tartrazine in experimental rats. Therefore, different doses of tartrazine alone and along with melon seed oil were given to experimental rats for a period of 60 days. The rats were killedat 20, 40 and 60 days of experiment and blood was collected and analyzed for various hematological and serological parameters. No mortality and behavioral changes were recorded though out the experiment. The results exhibited significant decrease in hematological parameters (hemoglobin and hematocrit), serum lipid profile (cholesterol, triglycerides, low density lipoprotein and high-density lipoprotein) and serum proteins (albumin, total proteins). Results revealed significantly higher levels of liver function tests (aspartate aminotransferase, alanine aminotransferase, bilirubin), renal function tests (urea, creatinine), cardiac enzymes (LDH, CPK and CK-Mb) and malondialdehyde (MDA) in response to various treatments of tartrazine. Different doses of melon seed oil used in current experimental research partially reversed the toxic effectsof tartrazine in experimental rats.
Monitoring and investigation of different toxic effects of frequently used food additives is of vital importance for public health. Tartrazine is an artificial food coloring compound and is extensively used in numerous food items to enhance their aesthetic value. The mechanism of toxic effects of tartrazine is not clear and is under debate. Hence, present work was planned to evaluate the toxicity of tartrazine and to assess the potential of melon seed oil to alleviate the toxic effects of tartrazine in experimental rats. Therefore, different doses of tartrazine alone and along with melon seed oil were given to experimental rats for a period of 60 days. The rats were killed at 20, 40 and 60 days of experiment and blood was collected and analyzed for various hematological and serological parameters. No mortality and behavioral changes were recorded though out the experiment. The results exhibited significant decrease in hematological parameters (hemoglobin and hematocrit), serum lipid profile (cholesterol, triglycerides, low density lipoprotein and high-density lipoprotein) and serum proteins (albumin, total proteins). Results revealed significantly higher levels of liver function tests (aspartate aminotransferase, alanine aminotransferase, bilirubin), renal function tests (urea, creatinine), cardiac enzymes (LDH, CPK and CK-Mb) and malondialdehyde (MDA) in response to various treatments of tartrazine. Different doses of melon seed oil used in current experimental research partially reversed the toxic effects of tartrazine in experimental rats.
Current guidelines recommend the use of lipid lowering agents based on the patient's cardiovascular risk. However numerous evidences demonstrate the presence of atherosclerotic alterations in patients identified as low risk. Molecules capable of acting on lipid metabolism with reduced side effects could be used for early treatment in this type of patients. We have conducted a prospective, open-label randomized controlled parallel group study to compare efficacy and safety of two different lipid lowering nutraceutical compounds: Liposcudil (R) and Lzposcudil PLUS. We selected patient with hypercholesterolemia and a low global cardiovascular risk. We evaluated the effect on lipid profile, inflammatory state and endothelial function. We observed a significant decrease in both group in total and low density lipoprotein cholesterol. No significant variations on triglycerides and high-density lipoprotein cholesterol. Efficacy on the inflammatory profile, evaluated through measurement of plasmatic high sensitivity C-reactive protein, interleukin-6, oxidized low density lipoprotein and tumor necrosis factor-alpha, was similar between the two group. An improvement of reactive hyperemia index, assessed using EndoPAT 2000 device, was found for both group. These data suggest that nutraceutical compounds are able to significantly improve the lipid and inflammatory profile as well as the endothelial function. No significant side effects were evidenced with this treatment.
Background
Obesity-related metabolic syndrome is associated with high incidence of cardiovascular diseases partially consecutive to vascular dysfunction. Therapeutic strategies consisting of multidisciplinary interventions include nutritional approaches. Benefits of supplementation with a specific melon concentrate, enriched in superoxide dismutase (SOD), have previously been shown on the development of insulin resistance and inflammation in a nutritional hamster model of obesity.
Objective
We further investigated arterial function in this animal model of metabolic syndrome and studied the effect of melon concentrate supplementation on arterial contractile activity.
Design and results
The study was performed on a hamster model of diet-induced obesity. After a 15-week period of cafeteria diet, animals were supplemented during 4 weeks with a specific melon concentrate (Cucumis melo L.) Contractile responses of isolated aorta to various agonists and antagonists were studied ex vivo. Cafeteria diet induced vascular contractile dysfunction associated with morphological remodeling. Melon concentrate supplementation partially corrected these dysfunctions; reduced morphological alterations; and improved contractile function, especially by increasing nitric oxide bioavailability and expression of endogenous SOD.
Conclusions
Supplementation with the specific melon concentrate improves vascular dysfunction associated with obesity. This beneficial effect may be accounted for by induction of endogenous antioxidant defense. Such an approach in line with nutritional interventions could be a useful strategy to manage metabolic syndrome–induced cardiovascular trouble.
Currently, there is significant interest among scientists and society as a whole with respect to human health as affected by diet. In particular, there is a significant push to identify mechanisms and ways fresh fruits and vegetables can help humans combat many of the health problems that currently exist. It has become apparent even in this age that synthetic pharmaceuticals are not always capable of sufficiently managing problems such as high blood pressure and cholesterol. The use of diet is becoming increasingly necessary with the high amount of cardiovascular disease in this country and throughout other places in the world. There have been various species identified that contain secondary compounds potentially beneficial to human health. In this chapter, we will focus on species in the family, Cucurbitaceae. Specifically, we will discuss the scientific literature regarding benefits associated with the consumption of crops such as watermelon and cantaloupe and how they impact cardiovascular health.
Antioxidants could be a therapy against obesity. We investigated whether a melon juice extract rich in superoxide dismutase activity would prevent its development in hamsters. Three groups received either a standard diet or a high fat diet (HF) plus a daily gavage with water (Control) or extract. After 12 weeks, the extract lowered triglyceridemia (67 percent), liver superoxide anion production (11 percent), lipid and protein oxidation products (35 and 35.7 percent), leptinemia (29 percent) and increased adiponectinemia (22 percent), leading to a concomitant reduction in insulinemia (39 percent), insulin resistance (41 percent) and abdominal lipids (28 percent). It decreased liver lipids (71 percent) and fully prevented the steatohepatitis induced by HF diet. Functional foods containing this melon extract could be an important new therapy to prevent obesity.
This paper reviews the recent research progress on the utilization of natural drugs against nonalcoholic fatty liver diseases(NAFLD)and alcoholic fatty liver diseases (AFLD). A total of 122 species of natural drugs, confined to the effective extracts of single herbal or animal drug and the active single natural products, were summarized and categorized as alkaloids, total flavonoids and total phenolics, single phenolics, terpenoids and steroids, total glycosides and total esters, amino acids and heterocycles, polysaccharides and proteoglycans, polypeptides/glycopeptides and poly-unsaturated fatty acids, coumarins and phenomens, single herbal drug, animal and fungus drugs. The future tendency of new natural drug research and development against NAFLD and AFLD is also discussed and some afforded suggestions were provided.
Oxidative stress is defined as an imbalance between antioxidants and reactive oxygen species (ROS) in favor of the latter. Under physiological conditions, ROS are continuously produced at low concentrations in the body, and they play an important role mostly by acting as second messengers to regulate key cellular responses. Various pathological conditions are characterized by a nonphysiological increased formation of ROS, which promotes cell dysfunction that can ultimately lead to irreversible cell lesions through oxidative alterations to lipids, DNA, and proteins. This chapter provides an overview of the major groups of natural antioxidants including vitamins, polyphenols, carotenoids, small antioxidant molecules, enzymes, and trace elements.
This chapter overviews the abiotic stressors that have, and potentially could be used as treatments, pre-and/or postharvest, to enhance the levels of bioactive compounds found in commonly cultivated fruit crops. First, the chapter describes the main groups of fruit bioactives sensitive to environmental stressors and their associations with human health. Next, it describes the main environmental stressors that can influence the levels of bioactives in fruits. Further, the chapter explains the influence of environmental stressors and other treatments on the levels of bioactives in some commercially important fruits. Finally, the recently proposed concept of xenohormesis, a principle that attempts to explain how stressed plant produce could be of benefit to the animals that consume it, is briefly discussed with respect to crop production and human health.
Benjamin Franklin, America’s greatest citizen, a printer by trade, scientist and philosopher by fame said, “Women & Melons are difficult to understand”. Musk melon (Cucumis melo) is a beautiful, juicy, tasty fruit of the Cucurbitaceae family, which includes 825 species in 118-119 genera. This family contains all the edible gourds, such as cucumbers, watermelons, Musk melons, squash, and pumpkins. Musk melon is cultivated in all tropical and subtropical areas of the world for its nutritional and medicinal value. The fruit is commonly known as Kharbooja in Hindi and Musk melon or Cantaloupe in English. The phytoconstituents from various parts of the plant include β-carotenes, apocaretenoids, ascorbic acid, flavonoids, terpenoids, chromone derivatives, carbohydrates, amino acids, fatty acids, phospholipids, glycolipids, volatile components and various minerals. Cucumis melo has been shown to possess useful medicinal properties such as analgesic, anti-inflammatory, anti-oxidant, free radical scavenging, anti-platelet, anti-ulcer, anti-cancer, anti-microbial, hepato-protective, diuretic, anti-diabetic, anthelmintic and anti-fertility activity. Thus, it is evident that Musk melon fruit possess a wide range of useful medicinal properties, which can be exploited clinically. The present review article covers comprehensively up-to-date information on the chemical constituents and medicinal profile of Musk melon.
Abstract Fatigue is defined as a decline in the ability and efficiency of mental and/or physical activities that is caused by excessive mental and/or physical activities. Fatigue can be classified as physical or mental. Mental fatigue manifests as potentially impaired cognitive function and is one of the most significant causes of accidents in modern society. Recently, it has been shown that the neural mechanisms of mental fatigue related to cognitive task performance are more complex than previously thought and that mental fatigue is not caused only by impaired activity in task-related brain regions. There is accumulating evidence supporting the existence of mental facilitation and inhibition systems. These systems are involved in the neural mechanisms of mental fatigue, modulating the activity of task-related brain regions to regulate cognitive task performance. In this review, we propose a new conceptual model: the dual regulation system of mental fatigue. This model contributes to our understanding of the neural mechanisms of mental fatigue and the regulatory mechanisms of cognitive task performance in the presence of mental fatigue.
Abstract We assessed the influence of SODB, a melon superoxide dismutase (SOD), on left ventricular (LV) hypertrophy in SHR. SODB (4 or 40U SOD) was given orally for 4 or 28 days to SHR. For each treatment period, LV weight index (LVWI) and cardiomyocytes size were measured. SOD, glutathione peroxidase (GPx) and catalase expressions, and LV production and presence of superoxide anion were determined. Pro-inflammatory markers were also measured. SODB reduced LVWI and cardiomyocytes size after 4 or 28 days. Cardiac SOD and GPx increased by 30-40% with SODB. The presence but not production of superoxide anion was significantly reduced by SODB. No effect of SODB was detected on inflammatory status in any group. The beneficial effect of SODB on cardiac hypertrophy seems to be related to the stimulation of endogenous antioxidant defense, suggesting that SODB may be of interest as a dietary supplementation during conventional antihypertensive therapy.
High-fat (HF) diets contribute to the development of cardiovascular diseases and the metabolic syndrome. This study was undertaken to investigate the beneficial effects of Vineatrol®-enriched red wines on blood lipids, oxidative stress and inflammation, and the role of some metabolic pathway regulatory proteins.
Golden Syrian hamsters received an HF diet for 13 wk, in the presence or absence of red wines supplemented with Vineatrol® (RWV) or not. The HF diet increased plasma cholesterol, triglycerides, glucose, and insulin, which were attenuated by RWV treatment. RWV protected against the HF-induced increase in liver nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and spared antioxidant enzyme activities. RWV did not reduce either liver steatosis or increased plasma leptin due to the HF diet, but greatly improved adiponectinemia. In the liver, RWV affected the inflammatory response by decreasing polymorphonuclear cell number and lowering TNF-α and IL-6 levels. Moreover, the increase in NF-κB activity in the HF group liver was prevented by RWV. Finally, RWV partially corrected low SIRT1 levels due to the HF diet but had no influence on SIRT3 or p-AMPK protein levels.
Our studies suggest that RWV is capable of reversing the atherogenic process induced by an HF diet in hamster tissues.
Background
The use of statins has allowed significant progress in the management of risk factors and a striking reduction of deaths from coronary disease. Nevertheless, more widespread use of statins is restricted by side effects and the refusal of patients.
Design
A prospective open label trial.
Methods
We investigated the effects of a combination of natural lipid-lowering and antioxidant agents containing policosanols from rice (10 mg), red yeast rice (200 mg), Extramel® (5 mg), phytosterols (50 mg), polyphenols from olive (10 mg), polyphenols from grape seed (10 mg) and folic acid (0.2 mg) on 60 hypercholesterolaemic patients.
Results
After 12 weeks the therapy produced an −11% average change from baseline in total cholesterol (total-C) levels (from 253.8±30.6 to 227.2±33.7 mg/dl, p<0.0001). The average low-density lipoprotein cholesterol (LDL-C) reduction was about 18% (from 169.3±35.8 to 144.4±31.7 mg/dl, p<0.0001). The changes in high-density lipoprotein cholesterol and triglycerides were not statistically significant. After 24 weeks these results were maintained, with a further small reduction of total-C levels and LDL-C levels.
Conclusions
A combination of natural active lipid-lowering agent and antioxidant agents induced a significant reduction in total-C and LDL-C levels after 12 weeks of treatment; the effect was maintained at 24 weeks, with no side effects during the whole observation.
Oxidative stress, involved in many diseases, is defined as an impaired balance between reactive oxygen species (ROS) production and antioxidant defences. Antioxidant enzymes such as superoxide dismutase (SOD) play a key role in diminishing oxidative stress. Thus, the removal of ROS by exogenous SODs could be an effective preventive strategy against various diseases. The poor bioavailability of exogenous SODs has been criticized. However, improvements in SOD formulation may overcome this limitation and boost interest in its therapeutic properties. Here, we provide a review of animal and human studies about SODs supplementation in order to evaluate their therapeutic value. Protective effects have been observed against irradiation, carcinogenesis, apoptosis and neurodegeneration. SODs administration has also been reported to alleviate inflammatory, infectious, respiratory, metabolic and cardiovascular diseases and genitourinary and fertility disorders, raising the question of its mechanism of action in these diverse situations. Some authors have shown an increase in endogenous antioxidant enzymes after exogenous SODs administration. The induction of endogenous antioxidant defence and, consequently, a decrease in oxidative stress, could explain all the effects observed. Further investigations need to be carried out to test the hypothesis that SODs supplementation acts by inducing an endogenous antioxidant defence.
We evaluated the effect of the intake of a grapevine-shoot phenolic extract (Vineatrol 30) on early atherosclerosis in hamsters fed a hyperlipidic diet. Golden Syrian hamsters received for 13 weeks either a standard diet, a high-fat (HF) diet, or the HF diet plus Vineatrol 30 at 0.04, 0.2, or 1.0 mg/(kg body weight/d). We measured plasma lipids and glucose, insulin, leptin and adiponectin, as well as liver TNF-α and IL-6 levels. Oxidative stress was assessed by measuring plasma paraoxonase activity (PON) and liver superoxide anion production (O(2)(•-)). The aortic fatty streak area (AFSA) was also determined. In comparison with HF group, we demonstrated that the highest dose of Vineatrol 30 was capable of decreasing AFSA (67%), insulinemia (40%), and leptinemia (8.7%), which were increased by the HF diet. We also showed increased O(2)(•-) production (35%) and a rise in levels of the liver proinflammatory cytokines TNF-α (22%) and IL-6 (21%), accompanied by a fall in PON activity (56%) due to the HF diet versus the standard diet. In contrast, except plasma adiponectin levels that are not changed, Vineatrol 30 treatment lowered AFSA (67%), O(2)(•-) production (36%), insulin resistance (42%), leptinemia (9%), liver TNF-α (18%) and IL-6 (15%), while it rose PON activity (29%). These findings demonstrate the preventive effects of polyphenols present in Vineatrol 30 in managing cardiovascular, metabolic, and inflammatory risk factors.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide and is closely associated with metabolic syndromes, such as obesity, diabetes, and insulin resistance. Nonalcoholic fatty liver (NAFL), also called simple steatosis, is the initial phase of NAFLD, which is accompanied the characteristic pathological overaccumulation of lipids without inflammation. To prevent NAFLD from reaching the NAFL stage through dietary therapy, in the present work, wild Chinese blueberries (Vacciniun spp.) were selected for their well-known benefits in inhibiting metabolic syndrome. After being purified from wild Chinese blueberries, polyphenol-rich extracts were subsequently separated into three fractions, namely, anthocyanin-rich fraction, phenolic acid-rich fraction, and ethyl acetate extract. The inhibition of oleic acid (OA)-induced triglyceride (TG) deposition in HepG 2 cells was referred to as the potential activity of preventing NAFL. Biochemical indicators, such as cytotoxicity, TG level, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and intracellular reactive oxygen species, were used to evaluate the analogous pathological stage of NAFLD. The results show that OA ≤ 1.0 mM exhibits a dose-dependent induction of TG accumulation, and no inflammation was observed based on the changes in ALT and AST levels. Therefore, 1.0 mM OA was used to simulate an in vitro fatty liver. Blueberry polyphenol-rich extract efficiently inhibited OA-induced TG accumulation in HepG2 cells, and the phenolic acid-rich fraction performed efficiently. Seven phenolic acids were subsequently identified using a high-performance liquid chromatography assay, and the main types were caffeic, chlorogenic, ferulic, p-coumaric, and cinnamic acids. These phenolic acid standards also displayed good efficiency in inhibiting TG accumulation in HepG2 cells. These results imply that wild Chinese blueberries have a potential preventive effect on NAFLD in its early stage, and phenolic acids are the most efficient component.
The potential benefits to health of antioxidant enzymes supplied either through dietary intake or supplementation is still a matter of controversy. The development of dietary delivery systems using wheat gliadin biopolymers as a natural carrier represents a new alternative. Combination of antioxidant enzymes with this natural carrier not only delayed their degradation (i.e. the superoxide dismutase, SOD) during the gastrointestinal digestive process, but also promoted, in vivo, the cellular defences by strengthening the antioxidant status. The effects of supplementation for 28 days with a standardized melon SOD extract either combined (Glisodin®) or not with gliadin, were evaluated on various oxidative-stress biomarkers. As already described there was no change either in superoxide dismutase, catalase or glutathione peroxidase activities in blood circulation or in the liver following non-protected SOD supplementation. However, animals supplemented with Glisodin® showed a significant elevation in circulated antioxidant enzymes activities, correlated with an increased resistance of red blood cells to oxidative stress-induced hemolysis. In the presence of Sin-1, a chemical donor of peroxynitrites, mitochondria from hepatocytes regularly underwent membrane depolarization as the primary biological event of the apoptosis cascade. Hepatocytes isolated from animals supplemented with Glisodin® presented a delayed depolarization response and an enhanced resistance to oxidative stress-induced apoptosis. It is concluded that supplementation with gliadin-combined standardized melon SOD extract (Glisodin®) promoted the cellular antioxidant status and protected against oxidative stress-induced cell death. Copyright © 2004 John Wiley & Sons, Ltd.
For sixteen years, the American institute of Nutrition Rodent Diets, AIN-76 and AIN-76A, have been used extensively around the world. Because of numerous nutritional and technical problems encountered with the diet during this period, it was revised. Two new formulations were derived: AIN-93G for growth, pregnancy and lactation, and AIN-93M for adult maintenance. Some major differences in the new formulation of AIN-93G compared with AIN-76A are as follows: 7 g soybean oil/100 g diet was substituted for 5 g corn oil/ 100 g diet to increase the amount of linolenic acid; cornstarch was substituted for sucrose; the amount of phosphorus was reduced to help eliminate the problem of kidney calcification in female rats; L-cystine was substituted for DL-methionine as the amino acid supplement for casein, known to be deficient in the sulfur amino acids; manganese concentration was lowered to one-fifth the amount in the old diet; the amounts of vitamin E, vitamin K and vitamin B-12 were increased; and molybdenum, silicon, fluoride, nickel, boron, lithium and vanadium were added to the mineral mix. For the AIN-93M maintenance diet, the amount of fat was lowered to 40 g/kg diet from 70 g/kg diet, and the amount of casein to 140 g/kg from 200 g/kg in the AIN-93G diet. Because of a better balance of essential nutrients, the AIN-93 diets may prove to be a better choice than AIN-76A for long-term as well as short-term studies with laboratory rodents.
The effects of a red wine phenolic extract (PE) on plasma lipoproteins and early atherosclerosis were studied in hamsters. Hamsters (n = 32) were divided into 4 groups of 8 and fed an atherogenic diet for 8 wk. They received by force- feeding 7.14 mL/(kg. d) PE in 2.6 mol/L ethanol (E + PE) or PE in water (W + PE), mimicking a moderate consumption of red wine or alcohol-free red wine [30.4 mg/(kg. d)], or 2.6 mol/L ethanol (E-PE) or water (W-PE) as their respective controls. Plasma cholesterol and triglyceride concentrations were lower in groups that consumed PE. The decrease in plasma apolipoprotein (Apo) B concentration was due mainly to PE and was significantly lower in Group E + PE than in Group E-PE (-7.5%) and in Group W + PE than in Group W-PE (-40%). Apo-A1 was not affected. PE significantly increased plasma antioxidant capacity by 9% in Group E + PE and 18% in Group W + PE compared with their respective controls. Liver glutathione peroxidase activity was 67% greater in the group receiving PE in water compared with the group given water; there was no effect when PE was given in ethanol relative to its control. Aortic fatty streak area (AFSA) was significantly reduced in the groups receiving PE in ethanol (-32%) or PE in water (-29%) in comparison with their respective controls. Ethanol significantly reduced AFSA by 60% (Group E-PE vs. Group W-PE) or 62% (Group E + PE vs. Group W + PE). These data suggest that ethanol is a complementary component of phenolics in the benefits of red wine for hamsters and that chronic ingestion of PE in ethanol prevents the development of atherosclerosis through several mechanisms. With moderate consumption of red wine, ethanol can improve the effects of phenolic compounds. However, alcohol-free red wine appears to be a very good alternative to red wine.
In a prospective, double-blind, randomised placebo-controlled study, we tested the hypothesis that a new formulation consisting of wheat gliadin chemically combined with a vegetal (thus orally effective) preparation of superoxide dismutase (SOD) allows to prevent hyperbaric oxygen (HBO)-induced oxidative cell stress. Twenty healthy volunteers were exposed to 100% oxygen breathing at 2.5 ATA for a total of 60 min. DNA strand breaks (tail moments) were determined using the alkaline version of the comet assay. Whole blood concentrations of reduced (GSH) and oxidised (GSSG) glutathione and F2-isoprostanes, SOD, glutathione peroxidase (GPx) and catalase (Cat) activities and red cell malondialdehyde (MDA) content were determined. After HBO exposure the tail moment (p = 0.03) and isoprostane levels (p = 0.049) were significantly lower in the group that received the vegetal formulation. Neither SOD and Cat nor GSH and GSSG were significantly affected by this preparation or HBO exposure. By contrast, blood GPx activity, which tended to be lower in the SOD-group already before the HBO exposure (p = 0.076), was significantly lower afterwards (p = 0.045). We conclude that an orally effective SOD-wheat gliadin mixture is able to protect against DNA damage, which coincided with reduced blood isoprostane levels, and may therefore be used as an antioxidant.
The consumption of fruit and vegetables is associated with a reduced rate of coronary heart disease (CHD) in observational cohorts. The purpose of this study was to assess the strength of this association in a meta-analysis. Cohort studies were selected if they reported relative risks (RRs) and 95% CI for coronary heart disease or mortality and if they presented a quantitative assessment of fruit and vegetable intake. The pooled RRs were calculated for each additional portion of fruit and/or vegetables consumed per day, and the linearity of the associations were examined. Nine studies were eligible for inclusion in the meta-analysis that consisted of 91,379 men, 129,701 women, and 5,007 CHD events. The risk of CHD was decreased by 4% [RR (95% CI): 0.96 (0.93-0.99), P = 0.0027] for each additional portion per day of fruit and vegetable intake and by 7% [0.93 (0.89-0.96), P < 0.0001] for fruit intake. The association between vegetable intake and CHD risk was heterogeneous (P = 0.0043), more marked for cardiovascular mortality [0.74 (0.75-0.84), P < 0.0001] than for fatal and nonfatal myocardial infarction [0.95 (0.92-0.99), P = 0.0058]. Visual inspection of the funnel plot suggested a publication bias, although not statistically significant. Therefore, the reported RRs are probably overestimated. This meta-analysis of cohort studies shows that fruit and vegetable consumption is inversely associated with the risk of CHD. The causal mechanism of this association, however, remains to be demonstrated.
The effects of spirulina and its chromophore phycocyanin, both without bound Se or selenium-enriched, were studied on plasma cholesterol, early atherosclerosis, cardiac production of superoxide anions, and NAD(P)H oxidase expression in hamsters. Forty hamsters were divided into 5 groups of 8 and fed an atherogenic diet for 12 weeks. They received by gavage either 7.14 mL/(kg day) phycocyanin (PC), Se-rich phycocyanin (SePC), spirulina (SP) or Se-rich spirulina (SeSP) in water, or water as control. SeSP and SePC supplied 0.4 microg of Se per 100 g body weight. Plasma cholesterol and non-HDL cholesterol concentrations were lower in group consuming SePC. HDL-cholesterol was never affected. SePC significantly increased plasma antioxidant capacity by 42% compared with controls. A sparing effect in liver glutathione peroxidase (87% on average) and superoxide dismutase (56% on average) activity was observed for all the groups compared to controls. Aortic fatty streak area was significantly reduced in the experimental groups, especially by PC (82%) and SePC (85%). Cardiac production of superoxide anion significantly decreased by approximately 46-76% in the four experimental groups and especially in SePC group (76%). The expression of p22phox subunit of NAD(P)H oxidase decreased by 34% after consumption of SePC. The results indicate that chronic consumption of Se-rich spirulina phycocyanin powerfully prevents the development of atherosclerosis. The underlying mechanism is related mainly to inhibiting pro-oxidant factors and at a lesser extent improving the serum lipid profile.
The concept according to which oxygen indispensable for the life of aerobic organisms can lead to cellular damages through the production of reactive oxygen species (e.g. the famous “free radicals”), only starts to be accepted by the medical field. A large number of epidemiological studies have indicated that reactive oxygen species (ROS) are implicated in the development of numerous pathological process such as atherosclerosis and cancerogenesis. To be protected against the toxicity of oxygen, our organism has developed antioxidant defences including enzymes (e.g. glutathion peroxidase), proteins (e.g. ferritin), vitamins (A, C, E) and trace elements (e.g. selenium). In physiological state, all these antioxidants have the capacity to perfectly regulate the production of ROS. An oxidative stress will be defined when there is an unbalance between prooxidants and antioxidants in favour of the formers. Each individual has not the same antioxidant potential due to differences in life style (e.g. smoking), diet, genetic morphology and environmental conditions of living. Actually, more and more importance is given to the determination of oxidative stress status as a tool allowing the prevention of some diseases. This is suggested by numerous in vivo studies showing that people with poor plasma concentrations in antioxidants (vitamins A, C and E) or elevated levels in oxidative markers of lipids have a higher risk to develop cardiovascular diseases or cancer than people with a diet balanced in fruits and vegetables. Under the control of health professionals, a supplementation in antioxidants could be given in order to prevent diseases in which oxidative stress is involved.
Evidence to support an important role of oxidative modification in mediating the atherogenicity of LDL continues to grow. New hypotheses suggest mechanisms by which Ox-LDL or products of Ox-LDL can affect many components of the atherogenic process, including vasomotor properties and thrombosis, as well as lesion initiation and progression itself. These ideas suggest new approaches, that in combination with lowering of plasma cholesterol, could lead to the prevention of atherosclerosis and its complications.
Limited dose-response curves for superoxide dismutase (SOD) were assessed in isolated and in vivo hearts. SOD at 2.3, 7, 20, or 50 mg/L suppressed CK release in Langendorff rat hearts by 61%, 63%, 72%, and 30%, respectively. SOD at 0.5, 1, 5, and 50 mg/L suppressed LDH release in Langendorff rabbit hearts by 32%, 48%, 54%, and -12%, respectively. In rabbit hearts subjected to coronary artery ligation and reperfusion in vivo, SOD at 2, 5, or 15 mg/kg reduced infarct size by 10%, 30% or 19%, respectively, while 50 mg/kg increased infarct size by 28%. In conclusion, while SOD was protective at low doses in all models, protection was lost at higher doses in the isolated rat and rabbit hearts, and exacerbation of damage was seen in the in vivo rabbit hearts.
This article is a brief overview of the mechanisms of production of reactive oxygen species in biologic systems, and the various antioxidant defense systems that provide protection against oxidative damage to biologic macromolecules. The mechanisms of lipid peroxidation and antioxidant protection are explained using a specific example, viz., oxidative modification of human low density lipoprotein and its prevention by vitamin C, vitamin E, and beta-carotene.
Bovine Cu, Zn superoxide dismutase (SOD), conjugated to colloidal gold, was intravenously administered to rats and its distribution studied by electron microscopy. Liver was the preferential site of accumulation of gold-labelled SOD. Among liver cells types, Kupffer and endothelial cells showed the presence of the protein earlier than hepatocytes. Uptake by kidney showed slower kinetics than liver. No uptake by heart could be detected. The gold-labelled SOD was localized inside coated pits, coated vesicles and other non-coated endocytic compartments. Absence of binding by BSA-gold complexes and competition between free SOD and the gold-labelled one demonstrated the specificity of the uptake process. Our morphological evidences suggest that in vivo internalization of SOD occurs most likely through receptor-mediated endocytosis.
The kinetic behaviour of bovine erythrocyte Cu-Zn SOD was investigated in Sprague Dawley male rats after subcutaneous and oral administrations of doses ranging from 0 center dot 5 to 20 mg kg-1. Studies have been carried out with SOD and SOD encapsulated into liposomes containing or not containing ceramides. The maximum concentration (Cmax) in blood cell pellets ranged from 8 center dot 65 to 11 center dot 03 U/mg haemoglobin (Hb) after subcutaneous injection, and from 4 center dot 48 to 8 center dot 23 U/mg Hb after oral administration. The maximum concentrations were reached in 5 h (t max) for the two routes. Comparison between the areas under the curves (AUCs) obtained after subcutaneous and oral administration allowed the calculation of relative bioavailability (F'). The maximum bioavailability after oral administration was 14% for free SOD, 22% for SOD encapsulated into liposomes, and 57% when ceramides were added to liposomes. Poor SOD bioavailability was enhanced by liposome encapsulation, and ceramide addition seemed to be beneficial for oral encapsulated SOD administration.
In mice with genetically engineered high levels of plasma low density lipoprotein (LDL), we tested the hypothesis that an increase in the dietary content of monounsaturated fatty acids but not of polyunsaturated fatty acids would promote atherosclerosis. The mouse model used was an LDL receptor-null, human apoB100-overexpressing strain. Six experimental groups of 19 to 38 mice of both sexes were established when the animals had reached 8 weeks of age. For the next 16 weeks, individual groups were fed either a commercial diet or prepared diets including fat as 10% of energy, with 5 different fatty acid enrichment patterns including the following: saturated (sat), cis and trans monounsaturated (mono), and n-3 and n-6 polyunsaturated (poly). Highly significant differences (ANOVA, P<0. 0001) in LDL cholesterol (in mg/dL) were found, with the rank order at 16 weeks being trans mono (mean, 1390)>sat (922)=cis mono (869)=n-6 poly (868)>n-3 poly (652)>commercial diet (526). Significant elevations in very low density lipoprotein cholesterol were also found in the trans and cis mono and sat groups, and triacylglycerol concentrations were also elevated in all groups. High density lipoprotein cholesterol concentrations were consistently low (20 to 50 mg/dL) in all groups. Highly significant differences (ANOVA, P<0.0001) in atherosclerosis, quantified by measurement of aortic cholesteryl ester concentration (mg/g protein) among dietary fatty acid groups were found, with the order being trans mono (mean, 50.4)>sat (35.6)=cis mono (34.6)>n-6 poly (18. 3)=n-3 poly (9.7)=commercial diet (7.8). Therefore, in this mouse model of hypercholesterolemia, dietary cis or trans monounsaturated fat did not protect against atherosclerosis development, whereas aortic atherosclerosis in either of the polyunsaturated fat groups was significantly less than in the saturated fat group.
To reveal genetic risk factors of nonfamilial idiopathic cardiomyopathy (IDC) in Japanese, polymorphisms in the SOD2 and HLA-DRB1 genes were investigated in 86 patients and 380 healthy controls. There was a significant excess of homozygotes for the V allele [Val versus Ala (A allele), a polymorphism in the leader peptide of manganese superoxide dismutase at position 16] of the SOD2 gene in the patients compared with the controls (87.2% versus 74.7%, odds ratio = 2.30, p = 0.013, pc < 0.03), and a significant increase in the frequency of HLA-DRB1*1401 in the patients was confirmed (14.0% vs 4.5%, odds ratio = 3.46, p = 0.001, pc < 0.03). A two-locus analysis suggested that these two genetic markers (SOD2-VV genotype and DRB1*1401) may play a synergistic role in controlling the susceptibility to nonfamilial IDC. In addition, processing efficiency of Val-type SOD2 leader peptide in the presence of mitochondria was siginificantly lower than that of the Ala-type by 11 +/- 4%, suggesting that this lower processing efficiency was in part an underlying mechanism of the association between the SOD2-VV genotype and nonfamilial IDC.
Oxidized low-density lipoprotein (OxLDL) exerts proliferation and apoptosis in vascular cells, depending on its concentration and the duration of exposure. Recent studies indicate that [O(2)](-) is involved in cell cycle regulation and that OxLDL stimulates endothelial cells to produce [O(2)](-). This study examined the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as a potential source for [O(2)](-) in the proliferation-inducing activity of OxLDL in cultured human umbilical vein endothelial cells (HUVEC). Human LDL was oxidized by Cu(++), and proliferation of HUVEC was detected by 3H-thymidine incorporation. OxLDL (5 microg/ml) caused an increase in proliferation of HUVEC of 250 to 300%. OxLDL-induced proliferation was blocked by addition of the antioxidants superoxide dismutase and catalase, suggesting that enhanced [O(2)](-) formation was involved. Diphenylene iodonium (DPI, 1 microM), an inhibitor of NADPH oxidase, also prevented OxLDL-induced proliferation of HUVEC, indicating that NADPH oxidase was the source for enhanced [O(2)](-) formation. The OxLDL effect was mimicked by lysophosphatidylcholine (LPC, 10 microM), a compound formed during oxidation of LDL. LPC-induced proliferation was also prevented by coincubation with DPI. Treatment of HUVEC with [O(2)](-) generated by the xanthine/xanthine oxidase reaction resulted in proliferation as did treatment with OxLDL. As expected, this stimulation could not be blocked by DPI. With the use of the cytochrome c-assay, it was demonstrated that OxLDL and LPC enhanced [O(2)](-) formation in HUVEC (by factor 3.2 and by factor 3.5, respectively). Supporting the assumption that NADPH oxidase was the enzyme responsible for [O(2)](-) formation, cells transfected with antisense oligonucleotides for NADPH oxidase showed a significantly reduced [O(2)](-) formation after stimulation with OxLDL and LPC. OxLDL and its compound LPC induce proliferation of HUVEC through activation of NADPH oxidase. The active NADPH oxidase generates [O(2)](-), which mediates the proliferative effects.
To examine the effect of overexpression of human intracellular copper-zinc superoxide dismutase (CuZnSOD1) gene on fetal mice brain exposed to in-utero ischemic reperfusion injury.
Transient in-utero ischemia (7 min) was induced in pregnant transgenic mice overexpressing human CuZnSOD1 and wild-type mice by occluding the blood supply to the uterine artery on day 17 of pregnancy, followed by 24 hours of reperfusion. The level of lipid peroxidation in fetal mice brains was compared between the transgenic and non-transgenic (control) fetal mice. Motor and coordination skills of transgenic and control adult mice (six to eight months old) which were exposed to ischemic reperfusion injury in-utero were compared by the rope grip test and visible platform task.
We first measured CuZnSOD1 activity in the brains of the transgenic fetal mice and confirmed that the enzyme activity is 4.2-fold higher than control. We also established that ischemia reperfusion on day 17 of pregnancy led to increased level of TBARS (Thiobarbituric acid reactive substance) in brains of wild-type fetal mice when compared to sham operated mice (72.5 +/- 3.4 vs. 49.4 +/- 1.5 nmol/mg. p < 0.001). The increase was markedly accentuated in the CuZnSOD1 transgenic mice, and significantly higher compared to control mice exposed to ischemia-reperfusion (85.6 +/- 4.0 vs. 69.5 +/- 2.3 nmol/mg, p < 0.001). Moreover, we found that the transgenic mice that were subjected to in-utero ischemia reperfusion exhibited a significantly higher rate of failures in the rope grip test and poorer performance in the visible platform task, when compared to non-transgenic mice exposed to identical insult.
Oxygen free radicals play an important role in the pathogenesis of perinatal hypoxia. Overexpression of the enzyme CuZnSOD1 in transgenic mice exposed their brains to increased damage during ischemic-reperfusion insult.
Nonalcoholic fatty liver disease, frequently associated with obesity, can lead to nonalcoholic steatohepatitis (NASH) and cirrhosis. The pathophysiology of NASH is poorly understood, and no effective treatment is available. In view of a potential deleterious role for reactive oxygen species (ROS), we investigated the origin of ROS overproduction in NASH. Mitochondrial production of ROS and its alterations in the presence of antioxidant molecules were studied in livers from ob/ob mice that bear a mutation of the leptin gene and develop experimental NASH. N-acetyl-cysteine and the superoxide dismutase (SOD) mimics ambroxol, manganese [III] tetrakis (5,10,15,20 benzoic acid) (MnTBAP), and copper [II] diisopropyl salicylate (CuDIPS) were used to target different checkpoints of the oxidative cascade to determine the pathways involved in ROS production. Liver mitochondria from ob/ob mice generated more O(2)*- than those of lean littermates (P <.01). Ex vivo, all three SOD mimics decreased O(2)*- generation (P <.001) and totally inhibited lipid peroxidation (P <.001) versus untreated ob/ob mice. Those modifications were associated with in vivo improvements: MnTBAP and CuDIPS reduced weight (P <.02) and limited the extension of histological liver steatosis by 30% and 52%, respectively, versus untreated ob/ob mice. In conclusion, these data demonstrate deleterious effects of superoxide anions in NASH and point at the potential interest of nonpeptidyl mimics of SOD in the treatment of NASH in humans.
The present study was conducted to evaluate in vitro and in vivo the antioxidant and anti-inflammatory properties of a cantaloupe melon (Cucumis melo LC., Cucurbitaceae) extract (CME) selected for its high superoxide dismutase activity. Peritoneal macrophages were pre-activated in vitro with 300 IU of interferon-gamma (IFN-gamma) and were then challenged in culture with IgGl/anti-IgG1 immune complexes (IgG1IC) in presence of various CME extracts. The subsequent production of free radicals (superoxide anion, nitric oxide, and peroxynitrite) and of pro-(TNF-alpha) and anti-(IL-10) inflammatory cytokines was evaluated. The CME inhibited in a dose-dependent manner the production of superoxide anion with a maximal effect at 100 microg/ml. This inhibitory effect of CME appeared to be closely linked to the SOD activity because it was dramatically decreased after heat inactivation of the SOD activity (HI-CME). In addition, the CME inhibited the production of peroxynitrite strengthening the antioxidant properties of this CME rich in SOD activity. The production of the pro- and anti-inflammatory cytokines, namely TNF-alpha and IL-10, being conditioned by the redox status of macrophages we also evaluated the effect of CME and HI-CME on the IgG1IC-induced cytokine production. When the SOD activity was present in the CME it promoted the IgG1IC-induced production of IL-10 instead of TNF-alpha. These data demonstrated that, in addition to its antioxidant properties, the anti-inflammatory properties of the CME extract were principally related to its capacity to induce the production of IL-10 by peritoneal macrophages. The particular properties of wheat gliadin (Triticum vulgare, Poaceae) for the oral delivery of functional proteins led us to test it in a new nutraceutical formula based on its combination with the CME thus monitoring the SOD activity release during the gastro-intestinal digestive process. In these experiments C57BL/6 mice were supplemented orally everyday during 28 days with: (1) the placebo, (2) the CME extract alone, (3) the gliadin, (4) the CME/gliadin combination, or (5) the HI-CME/gliadin combination (SOD inactivated). At the end of the supplementation period all the animals were injected intra-peritoneal (i.p.) with the pro-inflammatory cytokine IFN-gamma (300 IU) and peritoneal macrophages were harvested 24 h after to test their capacities to produce free radicals, TNF-alpha and IL-10 after triggering with IgG1IC. We demonstrated that animals supplemented during 28 days with the CME/gliadin combination were protected against the pro-inflammatory properties of IFN-gamma while the other products were inefficient. These data did not only indicate that the SOD activity is important for the antioxidant and anti-inflammatory properties of the CME extract, but also demonstrated that when the SOD activity is preserved during the digestive process by its combination with wheat gliadin it is possible to elicit in vivo the pharmacological effects of this antioxidant enzyme.
Products of systemic lipid peroxidation are important in the pathogenesis of cardiovascular disease. Subjects with NASH have increased hepatic lipid peroxidation, but it is unknown if they have increased oxidative stress and lipid peroxidation systemically. Therefore, we conducted a study to measure the circulating levels of lipid peroxidation products and their metabolic and nutritional correlates in patients with NASH and controls.
Systemic lipid peroxidation was assessed by measuring the levels of oxidized LDL (ox-LDL) and thiobarbituric acid-reacting substances (TBARS) in 21 subjects with NASH and 19 controls. Correlations were made between serum lipid peroxidation and nutritional determinants of oxidative stress and defense, serum lipids, insulin resistance, transaminases, and liver histology. The short-term nutrient intake was analyzed by maintaining a 3-wk dietary diary.
The serum levels of ox-LDL were significantly higher in NASH patients compared to controls (56 +/- 16 U/L vs 40 +/- 12 U/L, respectively, p < 0.001). Similarly, serum TBARS were significantly higher in NASH patients compared to controls (3.4 +/- 1.3 vs 1.8 +/- 0.9 nmols/ml, respectively, p= 0.0001). Insulin resistance was independently associated with ox-LDL (p= 0.01) and TBARS levels (p= 0.01). We found no differences in the intake of various macro- and micronutrients between the two groups and there was no association between nutrient intake and ox-LDL or TBARS.
Subjects with NASH have significantly higher systemic levels of lipid peroxidation products and this could indicate an increased risk of cardiovascular disease. More studies are needed to evaluate this possibility.
Insulin resistance and oxidative stress act synergistically in the development of cardiovascular complications. The present study compared the efficacy of three polyphenolic extracts in their capacity to prevent hypertension, cardiac hypertrophy, increased production of reactive oxygen species (ROS) by the aorta or the heart, and increased expression of cardiac NAD(P)H oxidase in a model of insulin resistance. Rats were fed a 60%-enriched fructose food and were treated once a day (gavage) for 6 weeks with 10 mL/kg of water only (F group) or the same amount of solution containing a red grape skin polyphenolic extract enriched in anthocyanins (ANT), a grape seed extract enriched in procyanidins and rich in galloylated procyanidins (PRO), or the commercial preparation Vitaflavan (VIT), rich in catechin oligomers. All treatments were administered at the same dose of 21 mg/kg of polyphenols. Our data indicate that (a) the ANT treatment prevented hypertension, cardiac hypertrophy, and production of ROS, (b) the PRO treatment prevented insulin resistance, hypertriglyceridemia, and overproduction of ROS but had only minor effects on hypertension or hypertrophy, while (c) Vitaflavan prevented hypertension, cardiac hypertrophy, and overproduction of ROS. All polyphenolic treatments prevented the increased expression of the p91phox NADPH oxidase subunit. In summary, our study suggest that (a) the pathogeny of cardiac hypertrophy in the fructose-fed rat disease involves both hypertension and hyperproduction of ROS, (b) polyphenolic extracts enriched in different types of polyphenols possess differential effects on insulin resistance, hypertension, and cardiac hypertrophy, and (c) polyphenols modulate the expression of NAD(P)H oxidase.
The effects of the phenolic compounds catechin (Cat), quercetin (Qer), and resveratrol (Res) present in red wine on early atherosclerosis were studied in hamsters. Hamsters (n = 32) were divided into 4 groups of 8 and fed an atherogenic diet for 12 weeks. They received by force-feeding 7.14 mL/(kg of body wt.day) Cat, Qer, or Res in water [2.856 mg/(kg of body wt.day) for Cat and 0.1428 mg/(kg of body wt.dday) for Qer and Res], mimicking a moderate consumption of alcohol-free red wine (equivalent to that supplied by the consumption of about two glasses of red wine per meal for a 70 kg human), or water as control. Plasma cholesterol concentration was lower in groups that consumed phenolics than in controls. The increase in plasma apolipoprotein (Apo) A1 concentration was mainly due to Cat (26%) and Qer (22%) and to a lesser extent, but nonsignificantly, Res (19%). Apo-B was not affected. Plasma antioxidant capacity was not improved, and there was no sparing effect on plasma vitamins A and E. Plasma iron and copper concentrations were not modified nor were liver super oxide dismutase and catalase activities. A sparing effect of Qer on liver glutathione peroxidase activity appeared, whereas Cat and Res exhibited a smaller effect. Aortic fatty streak area was significantly reduced in the groups receiving Cat (84%) or Qer (80%) or Res (76%) in comparison with the controls. These findings demonstrate that catechin, quercetin, and resveratrol at nutritional doses prevent the development of atherosclerosis through several indirect mechanisms.
The purpose of the present study was to investigate whether the local prevention of luminal superoxide-mediated biological damage in the rat jejunal mucosa could be achieved by liposomal superoxide dismutase (SOD) and the SOD mimic tempamine (TMN). Cationic liposomes loaded with either SOD or TMN were perfused in the rat jejunum prior to the induction of oxidative insult. Reactive hydroxyl radicals were generated in situ in a closed circulating intestinal loop of the rat from the reaction between hypoxanthine and xanthine oxidase in the presence of chelated ferrous sulfate. Mucosal activity of lactate dehydrogenase and levels of potassium ions were used to quantify the tissue damage. Intracellular uptake and locality of SOD were examined in HT-29 cells. The intestinal uptake of SOD and TMN was further measured by using rat colon sacs. Entrapment in cationic liposomes was found to significantly enhance the antioxidant effect of SOD and TMN against the induced oxidative damage in the jejunal mucosa, compared with their free forms. The effect was found to be local and was caused by the increased mucosal adhesion of the liposomes. The cationic liposomes also triggered SOD uptake into the HT-29 cell line. It is concluded that the increased residence time of the cationic liposomes of SOD and TMN in the jejunal mucosa resulted in a local effect against oxidative injury. This local protection may be exploited for drug delivery purposes.
Obesity is not necessary to observe insulin resistance in humans since severe insulin resistance also characterizes patients lacking subcutaneous fat such as those with HAART (highly-active antiretroviral therapy) - associated lipodystrophy. Both the obese and the lipodystrophic patients have, however, an increase in the amount of fat hidden in the liver. Liver fat content can be non-invasively accurately quantified by proton magnetic resonance spectroscopy. It is closely correlated with fasting insulin and direct measures of hepatic insulin sensitivity while the amount of subcutaneous adipose tissue is not. The causes of interindividual variation in liver fat content independent of obesity are largely unknown but could involve differences in signals from adipose tissue such as in the amount of adiponectin produced and differences in fat intake. Adiponectin deficiency characterizes both lipodystrophic and obese insulin resistant individuals, and serum levels correlate with liver fat content. Liver fat content can be decreased by weight loss. In addition, treatment of both lipodystrophic and type 2 diabetic patients with PPARgamma agonists but not metformin decreases liver fat and increases adiponectin levels. Markers of liver fat such as serum alanine aminotransferase activity have been shown to predict type 2 diabetes in several studies independent of obesity. The fatty liver thus may help to explain why some but not all obese individuals are insulin resistant and why even lean individuals may be insulin resistant, and thereby at risk of developing type 2 diabetes and cardiovascular disease.
Chronic liver damage is a widespread pathology characterized by a progressive evolution from steatosis to chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. As the oxidative stress plays a central role in liver diseases pathogenesis and progression, the use of antioxidants have been proposed as therapeutic agents, as well as drug coadjuvants, to counteract liver damage. In this work in vitro and in vivo studies, with emphasis on humans and animals experiments, have been considered and reviewed according to antioxidant typologies. Great differences emerge as far as ingested doses, bioavailability and liver ability to accumulate the various compounds. Results available up to now suggest that lycopene-rich foods could be proposed in therapeutic treatment of some liver pathologies. On the other hand contradictory results have been obtained with alpha-tocopherol, beta-carotene and trans-resveratrol. Quercetin, silymarin, esculetin and thyme and rosemary among phenolic compounds need further studies.
Non-alcoholic fatty liver disease (NAFLD) is present in up to one-third of the general population and in the majority of patients with metabolic risk factors such as obesity and diabetes. Insulin resistance is a key pathogenic factor resulting in hepatic fat accumulation. Recent evidence demonstrates NAFLD in turn exacerbates hepatic insulin resistance and often precedes glucose intolerance. Once hepatic steatosis is established, other factors, including oxidative stress, mitochondrial dysfunction, gut-derived lipopolysaccharide and adipocytokines, may promote hepatocellular damage, inflammation and progressive liver disease. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies, however, staging the disease requires a liver biopsy. NAFLD is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as cirrhosis and hepatocellular carcinoma, which occur in a minority of patients. NAFLD is also now recognized to account for a substantial proportion of patients previously diagnosed with 'cryptogenic cirrhosis'. Diabetes, obesity and the necroinflammatory form of NAFLD known as non-alcoholic steatohepatitis, are risk factors for progressive liver disease. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Further research is needed to identify which patients will achieve the most benefit from therapy.
Diabetes is associated with increased oxidative stress and atherosclerosis development. In the present study, we investigated the effects of pomegranate juice (PJ; which contains sugars and potent anti-oxidants) consumption by diabetic patients on blood diabetic parameters, and on oxidative stress in their serum and macrophages. Ten healthy subjects (controls) and 10 non-insulin dependent diabetes mellitus (NIDDM) patients who consumed PJ (50ml per day for 3 months) participated in the study. In the patients versus controls serum levels of lipid peroxides and thiobarbituric acid reactive substances (TBARS) were both increased, by 350% and 51%, respectively, whereas serum SH groups content and paraoxonase 1 (PON1) activity, were both decreased (by 23%). PJ consumption did not affect serum glucose, cholesterol and triglyceride levels, but it resulted in a significant reduction in serum lipid peroxides and TBARS levels by 56% and 28%, whereas serum SH groups and PON1 activity significantly increased by 12% and 24%, respectively. In the patients versus controls monocytes-derived macrophages (HMDM), we observed increased level of cellular peroxides (by 36%), and decreased glutathione content (by 64%). PJ consumption significantly reduced cellular peroxides (by 71%), and increased glutathione levels (by 141%) in the patients' HMDM. The patients' versus control HMDM took up oxidized LDL (Ox-LDL) at enhanced rate (by 37%) and PJ consumption significantly decreased the extent of Ox-LDL cellular uptake (by 39%). We thus conclude that PJ consumption by diabetic patients did not worsen the diabetic parameters, but rather resulted in anti-oxidative effects on serum and macrophages, which could contribute to attenuation of atherosclerosis development in these patients.
A composition consisting of extracts of five widely studied medicinal plants (Protandim) was administered to healthy human subjects ranging in age from 20 to 78 years. Individual ingredients were selected on the basis of published findings of induction of superoxide dismutase (SOD) and/or catalase in rodents in vivo, combined with evidence of decreasing lipid peroxidation. Each ingredient was present at a dosage sufficiently low to avoid any accompanying unwanted pharmacological effects. Blood was analyzed before supplementation and after 30 and 120 days of supplementation (675 mg/day). Erythrocytes were assayed for SOD and catalase, and plasma was assayed for lipid peroxidation products as thiobarbituric acid-reacting substances (TBARS), as well as uric acid, C-reactive protein, and cholesterol (total, LDL, and HDL). Before supplementation, TBARS showed a strong age-dependent increase. After 30 days of supplementation, TBARS declined by an average of 40% (p = 0.0001) and the age-dependent increase was eliminated. By 120 days, erythrocyte SOD increased by 30% (p < 0.01) and catalase by 54% (p < 0.002). We conclude that modest induction of the catalytic antioxidants SOD and catalase may be a much more effective approach than supplementation with antioxidants (such as vitamins C and E) that can, at best, stoichiometrically scavenge a very small fraction of total oxidant production.
We previously reported in healthy volunteers that a cantaloupe melon extract chemically combined with wheat gliadin (melon extract/gliadin) and containing SOD, catalase and residual glutathione peroxidase (GPx), protected against DNA strand-break damage induced by hyperbaric oxygen (HBO), a well-established model of DNA damage resulting from oxidative stress. Aortic cross-clamping is a typical example of ischemia/reperfusion injury-related oxidative stress, and therefore we investigated whether this melon extract/gliadin would also reduce DNA damage after aortic cross-clamping and reperfusion.
Prospective, randomized, controlled experimental study.
Animal laboratory.
18 anesthetized, mechanically ventilated and instrumented pigs.
After 14 days of oral administration of 1250 mg of the melon extract/gliadin (n=9) or vehicle (n=9), animals underwent 30 min of thoracic aortic cross-clamping and 4 h of reperfusion.
Before clamping, immediately before declamping, and at 2 and 4 h of reperfusion, we measured blood isoprostane (immunoassay) and malondialdehyde concentrations (fluorimetric thiobarbituric acid test), SOD, catalase and GPx activities (spectrophotometric kits), NO formation (nitrate+nitrite; chemoluminescence), DNA damage in whole blood samples and isolated lymphocytes exposed to hyperbaric oxygen (comet assay). Organ function was also evaluated. Kidney and spinal cord specimen were analysed for apoptosis (TUNEL assay). The melon extract/gliadin blunted the DNA damage, reduced spinal cord apoptosis and attenuated NO release, however, without any effect on lipid peroxidation and organ function.
Pre-treatment with the oral melon extract/gliadin may be a therapeutic option to reduce oxidative cell injury affiliated with aortic cross-clamping.
The effects of fruit and vegetable extract (Oxxynea) on plasma cholesterol, early atherosclerosis, cardiac production of superoxide anion, and NAD(P)H oxidase expression were studied in an animal model of atherosclerosis. Thirty six hamsters were divided into two groups of 18 and fed an atherogenic diet for 12 weeks. They received by gavage either water or Oxxynea in water at a human dose equivalent of 10 fruits and vegetables per day. Oxxynea lowered plasma cholesterol and non-HDL cholesterol, but not HDL-cholesterol, and increased plasma antioxidant capacity. It also strongly reduced the area of aortic fatty streak deposition by 77%, cardiac production of superoxide anion by 45%, and p22phox subunit of NAD(P)H oxidase expression by 59%. These findings support the view that chronic consumption of antioxidants supplied by fruits and vegetables has potential beneficial effects with respect to the development of atherosclerosis. The underlying mechanism is related mainly to inhibiting pro-oxidant factors and improving the serum lipid profile.
Alcohol is a well-known risk factor for liver damage and is one of the major causes of liver disease worldwide. Chronic intake of alcohol, over a certain limit, inevitably leads to hepatic steatosis. If the injury persists, steatosis with concomitant tumor necrosis factor-alpha and other cytokines, progresses to steatohepatitis, fibrosis and finally cirrhosis. Among the multiple factors involved in the process of alcohol-induced liver injury, a crucial role is played by oxidative stress. Several mechanisms during ethanol metabolism result in reactive oxygen species (ROS) production. Although the main site of ethanol metabolism is hepatocytes, other mechanisms are involved in alcohol-induced liver injury. Specifically, in the ROS production activity, an important role is played by the NADPH oxidase complex. NADPH oxidase is expressed in hepatocytes, hepatic stellate cells and Kupffer cells in the liver. Studying NADPH oxidase gives new insights into alcohol-induced liver damage and provides new direction for future therapeutic strategies.
This study was designed to test the effect of antioxidant supplementation on feline immunodeficiency virus (FIV)-infected felines. Six acutely FIV-infected cats (> or =16 weeks post-inoculation) were given a propriety oral superoxide dismutase (SOD) supplement (Oxstrin; Nutramax Laboratories) for 30 days. Following supplementation, the erythrocyte SOD enzyme concentration was significantly greater in the supplemented FIV-infected group than the uninfected control group or the unsupplemented FIV-infected group. The CD4+ to CD8+ ratio increased significantly (0.66-0.88) in the SOD supplemented FIV-infected cats but not in the unsupplemented FIV-infected cats. Proviral load and reduced glutathione (GSH) levels in leukocyte cell types did not change significantly following supplementation. Antioxidant supplementation resulted in an increase in SOD levels, confirming the oral bioavailability of the compound in FIV-infected cats. This result warrants further investigation with trials of antioxidant therapy in FIV-infected cats that are showing clinical manifestations of their disease, as well as in other feline patients where oxidative stress likely contributes to disease pathogenesis, such as diabetes mellitus and chronic renal failure.
Fatty liver as a determinant of atherosclerosis
- Schwimmer Jb
- R Deutsch
- C Behling
- Lavine
- Je
Schwimmer JB, Deutsch R, Behling C, Lavine JE. Fatty liver as a determinant of atherosclerosis. Hepatology 2005;42(S1): 610A [abstract].
Dietary anti-oxidant compounds and liver health):575e86. A melon extract prevents atherosclerosis in hamsters
- P Vitaglione
- F Morisco
- N Caporaso
- Fogliano
Vitaglione P, Morisco F, Caporaso N, Fogliano V. Dietary anti-oxidant compounds and liver health. Crit Rev Food Sci Nutr 2004;44(7):575e86. A melon extract prevents atherosclerosis in hamsters
Guide for the care and the use of laboratory animals. Publication no. 85-23 (rev.). Bethesda, MD: National Institutes of Health
- Research National
- Council
National Research Council. Guide for the care and the use of laboratory animals. Publication no. 85-23 (rev.). Bethesda, MD: National Institutes of Health; 1985.
Role of oxidized lipoprotein in atherogenesis
- Witzum
Fatty liver as a determinant of atherosclerosis
- Schwimmer