Naringin alters the cholesterol biosynthesis and antioxidant enzyme activities in LDL receptor-knockout mice under cholesterol fed condition

The purpose of the current study was to evaluate the lipid lowering and antioxidant capacity of naringin in LDL receptor knockout (LDLR-KO) mice fed a cholesterol (0.1 g/100 g) diet. As such, naringin or lovastatin (0.02 g/100 g) was supplemented in a cholesterol diet for 6 weeks. The naringin and lovastatin supplementation significantly lowered the plasma total cholesterol level compared to the control group. The plasma and hepatic triglyceride level was only lowered by the lovastatin supplement, while the hepatic cholesterol content was lowered by both the naringin and lovastatin supplements compared to the control group. The hepatic HMG-CoA reductase activity was significantly lower in the naringin and lovastatin supplemented groups than in the control group, whereas the ACAT activity was unaffected. The excretion of total sterol was significantly higher in the naringin and lovastatin groups compared to the control group due to significant changes in the acidic and neutral sterol, respectively. When comparing the hepatic antioxidant enzyme activities, the superoxide dismutase, catalase, and glutathione reductase activities were all significantly higher in the naringin-supplemented group than in the control group, while only the lovastatin supplement increased the glutathione reductase activity. Accordingly, the current results confirmed that naringin lowers the plasma cholesterol level via the inhibition of hepatic HMG-CoA reductase activity and increases the excretion of fecal sterol. Naringin was also found to improve the activities of hepatic antioxidant enzymes against oxidative stress in a hypercholesterolemic animal model, i.e. cholesterol-fed LDLR-KO mice.     

Hazelnut oil administration reduces aortic cholesterol accumulation and lipid peroxides in the plasma, liver, and aorta of rabbits fed a high-cholesterol diet

Hazelnut oil (HO) is rich in monounsaturated fatty acids and antioxidants. We wanted to investigate the effect of HO on lipid levels and prooxidant-antioxidant status in rabbits fed a high-cholesterol (HC) diet. An HC diet caused significant increases in lipids and lipid peroxide levels in the plasma, liver, and aorta together with histopathological atherosclerotic changes in the aorta. Glutathione levels, glutathione peroxidase, and glutathione transferase activities decreased significantly, but superoxide dismutase activity and vitamin E and C levels remained unchanged in the livers of rabbits following HC diet. HO supplementation reduced plasma, liver, and aorta lipid peroxide levels and aorta cholesterol levels together with amelioration in atherosclerotic lesions in the aortas of rabbits fed an HC diet, without any decreasing effect on cholesterol levels in the plasma or liver. HO did not alter the antioxidant system in the liver in the HC group. Our findings indicate that HO reduced oxidative stress and cholesterol accumulation in the aortas of rabbits fed an HC diet.     

Antioxidative and hypolipidemic effects of diosgenin, a steroidal saponin of yam (Dioscorea spp.), on high-cholesterol fed rats

Diosgenin (a steroidal saponin of yam) has long been used as a raw material for the industrial production of steroid drugs, and reported to have a hypocholesterolemic effect by suppressing cholesterol absorption and increasing cholesterol secretion. Oxidative stress has been suggested as a main risk factor in the development of atherosclerosis. The aim of this study is to investigate the possible hypolipidemic and antioxidative effect of diosgenin on rats fed with a high-cholesterol diet supplemented with either 0.1% or 0.5% diosgenin for 6 weeks. We measured the lipid profile in the plasma and liver, lipid peroxidation and antioxidative enzyme activities in the plasma, erythrocyte and gene expression of antioxidative enzymes in the liver, and the oxidative DNA damage in lymphocytes. Diosgenin showed a decrease in the plasma and hepatic total cholesterol levels, but increased the plasma high-density lipoprotein (HDL) cholesterol level. Erythrocyte TBARS and lymphocyte DNA damage measured by the comet assay were decreased in the diosgenin supplemented group. Furthermore, diosgenin feeding enhanced the resistance to lymphocyte DNA damage caused by an oxidant challenge with H(2)O(2). The antioxidative enzyme activities were also affected by diosgenin supplementation. Total superoxide dismutase (SOD) in the plasma and liver, glutathione peroxidase (GSH-Px) in erythrocytes, and catalase (CAT) in erythrocytes and liver were significantly increased in the 0.5% diosgenin group. The expression of antioxidative enzymes was up-regulated by diosgenin, the expression of GSH-Px being the highest in the 0.5% diosgenin group. These results suggest that diosgenin could be a very useful compound to control hypercholesterolemia by both improving the lipid profile and modulating oxidative stress.     

Supplementation of naringenin and its synthetic derivative alters antioxidant enzyme activities of erythrocyte and liver in high cholesterol-fed rats

The antioxidative effects of naringenin (1) and its synthetic derivative, naringenin 7-O-cetyl ether (2), were tested. Male rats were fed a 1 g/100 g high-cholesterol diet for 6 weeks with supplements of either 1 or 2 (0.073 mmol/100 g diet) to study the effects on the antioxidant enzyme activities in the erythrocyte and liver. The erythrocyte catalase (CAT) and superoxide dismutase (SOD) activities were significantly higher in the compounds 1 or 2 supplemented groups than in the control group, whereas the hepatic SOD and CAT activities were significantly lower in the compound 2 supplemented group. The compounds 1 and 2 supplements to a high cholesterol diet lowered or tended to lower the plasma TBARS levels, that is, lipid peroxide products, while enhancing the plasma paraoxonase activity. These results indicate that the supplementation of 1 and 2 was effective in improving the antioxidant capacity of the erythrocyte and liver, plus the synthetic functional compound 2 appeared to be as potent as 1 in enhancing the antioxidant defense system.     

Effects of fish oil and vitamin E on the antioxidant defense system in diet-induced hypercholesterolemic rabbits

This study was designed to investigate the effects of fish oil and vitamin E on the antioxidant defense system in hypercholesterolemic rabbits. A high fat and cholesterol diet, with or without supplement by fish oil and/or a vitamin E supplement, was fed to rabbits for 6 weeks. Compared to the reference diet of regular laboratory rabbit chow, a high fat and cholesterol-enriched diet increased atheroma formation, plasma lipid and peroxide levels, decreased blood glutathione levels, and reduced plasma glutathione reductase, glutathione peroxidase, and catalase activities. Fish oil supplementation significantly reduced atheroma and increased glutathione reductase and glutathione peroxidase activities and blood glutathione levels, but increased plasma lipid peroxide levels. Vitamin E supplementation of the fish oil diet enhanced the beneficial effects by increasing glutathione reductase activity and decreasing peroxide levels. These results indicate that a high fat and cholesterol diet attenuates blood glutathione levels and plasma antioxidant enzyme activities, which may account for some of its atherogenic properties. Consumption of fish oil enhances antioxidative defenses against the oxidative stress imposed by hypercholesterolemia, and vitamin E further enhances these beneficial effects.     

Role of naringin supplement in regulation of lipid and ethanol metabolism in rats

The current study was performed to investigate the effect of naringin supplements on the alcohol, lipid, and antioxidant metabolism in ethanol-treated rats. Male Sprague-Dawley rats were randomly divided into six groups (n = 10) based on six dietary categories: ethanol and naringin-free, ethanol (50 g/L) plus low-naringin (0.05 g/L), ethanol plus high-naringin (0.125 g/L), and three corresponding pair-fed groups. The pair-fed control rats received an isocaloric diet containing dextrin-maltose instead of ethanol for 5 wks. Among the ethanol treated groups, the naringin supplements significantly lowered the plasma ethanol concentration with a simultaneous increase in the ADH and/or ALDH activities. However, among the ethanol-treated groups, naringin supplementation resulted in a significant decrease in the hepatic triglycerides and plasma and hepatic total cholesterol compared to that in the naringin-free group. Naringin supplementation significantly increased the HDL-cholesterol and HDL-C/total-C ratio, while lowering the AI value among the ethanol-treated groups. Hepatic lipid accumulation was also significantly reduced in the naringin-supplemented groups compared to the naringin-free group among the ethanol-treated groups, while no differences were found among the pair-fed groups. Among the ethanol-treated groups, the low-naringin supplementation resulted in a significant decrease in the levels of plasma and hepatic TBARS, whereas it resulted in higher SOD and GSH-Px activities and gluthathion levels in the liver. Accordingly, naringin would appear to contribute to alleviating the adverse effect of ethanol ingestion by enhancing the ethanol and lipid metabolism as well as the hepatic antioxidant defense system.     

Effect of 3,4-di(OH)-cinnamate synthetic derivative on plasma and hepatic cholesterol level and antioxidant enzyme activities in high cholesterol-fed rats

The effect of 3,4-di(OH)-phenylpropionic acid (L-phenylalanine methyl ester) amide (SL-1063), a synthetic derivative of 3,4-di(OH)-cinnamate, on the cholesterol metabolism and antioxidant enzyme system was examined in rats. Diets that included either SL-1063 (0.046%, w/w) or lovastatin (0.02%, w/w) as a supplement, plus 1 g cholesterol/100 g diet were fed to rats ad libitum for 5 weeks. The total plasma cholesterol and triglyceride levels were significantly lowered by the SL-1063 supplement compared to the control group. Meanwhile, the levels of plasma HDL-cholesterol and ratio of HDL-cholesterol/total cholesterol (%) were significantly higher in the SL-1063 group than in the control group. However, the lovastatin supplement did not affect the plasma lipid level. The hepatic cholesterol level and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity were significantly lowered in the lovastatin group compared to the SL-1063 group; however, the hepatic triglyceride level did not differ among the groups. The activity of hepatic acyl CoA: cholesterol acyltransferase (ACAT), the enzyme that catalyzes hepatic cholesterol esterification, was significantly lower in the lovastatin and SL-1063 groups than in the control group. Furthermore, the SL-1063 supplement elevated the excretion of fecal sterols. As regards the hepatic antioxidant enzyme system, the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR) activities were all significantly higher in the SL-1063 group compared to the control group, whereas only the GR activity was significantly increased by the lovastatin supplement. No marked difference in the GSH levels and glucose-6-phosphate dehydrogenase (G6PD) activities was observed among the groups. The levels of plasma and hepatic thiobarbituric acid reactive substances (TBARS) were lowered by the SL-1063 supplement compared to the control group. Accordingly, the current results suggest that SL-1063, a synthetic derivative of 3,4-di(OH)-cinnamate, is effective in lowering the plasma lipids and improving the antioxidant enzyme system.     

The effect of thymosin fraction 5 on lipid peroxidation in rabbits fed a high-cholesterol diet

Plasma and erythrocyte lipid levels and susceptibility of erythrocytes to lipid peroxidation were determined in rabbits fed diet containing 2% (w/w) cholesterol, for 3 months. Hypercholesterolemic rabbits had high plasma and erythrocyte lipid peroxide levels as compared to control rabbits. After high-cholesterol diet, the rabbits in the experimental group were divided into two groups. The first group was fed a normal diet for 21 days and the second group was given normal diet plus thymosin F5 injections every other day for the same period. At the end of this period, plasma and erythrocyte lipid peroxide levels were significantly decreased in the group injected with thymosin F5.     

Effect of a taurine treatment on the regression of existing atherosclerotic lesions in rabbits fed on a high-cholesterol diet

We studied whether taurine has any regressive effect on existing atherosclerotic lesions and lipid peroxidation in rabbits fed on a high-cholesterol (HC) diet. The cholesterol, triglyceride, malondialdehyde (MDA) and diene conjugate (DC) levels, as well as the aortic histopathological findings were examined in rabbits that had been fed on a cholesterol-containing diet for 8 months [0.5% cholesterol (w/w) for 3 months and subsequently 0.25% cholesterol (w/w) for 5 months], and then for a further 4 months on a normal diet with or without taurine treatment [1% (w/v) in the drinking water]. High levels of lipid and lipid peroxide induced by the HC diet were observed to decline in the plasma, liver and aorta of atherosclerotic rabbits, as well as a slight retardation in aortic atherosclerotic lesions during the regression period. Although no significant differences in the lipid and lipid peroxide levels in the plasma and aorta were found between the regressed groups with or without the taurine treatment, the extent of atherosclerotic lesions in the aorta was less in the taurine-treated regressed group than in the non-treated regressed group. However, the liver MDA and DC levels were lower in the regressed rabbits with the taurine treatment in the non-treated group. These results indicate that the taurine treatment may accelerate the regression of cholesterol-induced atherosclerotic lesions in rabbits without having any effect on the plasma and aorta lipid and lipid peroxide levels.     

A diet high in cholesterol and deficient in vitamin E induces lipid peroxidation but does not enhance antioxidant enzyme expression in rat liver

Expression of antioxidant enzymes (AOE), an important mechanism in the protection against oxidative stress, could be modified by the redox status of the cells. The aim of this project was to evaluate the role of vitamin E deficiency in association with a high-cholesterol diet in the hepatic lipid peroxidation and the expression of AOE. Two groups of 6 male rats were fed with a high-cholesterol or a high-cholesterol vitamin E-deficient diet. All animals were sacrificed at 72 days of treatment. Liver lipid peroxidation index (Malondialdehyde; MDA) and hepatic AOE were evaluated. Total liver RNA was extracted, and the steady state messenger RNA (mRNA) levels of glutathion peroxydase, manganese superoxide dismutase, Cu/Zn superoxide dismutase and catalase were examined by northern blot. After 72 days on the diet, a significant increase in the lipid peroxidation index was observed in the vitamin E deficient group (MDA : 4.45 +/- 0.29 nmol/mg protein versus 3.65 +/- 0.1 nmol/mg protein in vitamin E normal group). Despite this oxidative stress, the activities and mRNA levels of liver AOE were not significantly different in the 2 groups. These preliminary results show that chronic vitamin E deficiency associated with high cholesterol diet is able to increase lipid peroxidation without modulation of AOE expression and activity in the liver. This suggests that beneficial effects of dietary vitamin E are due to a plasma antioxidant effect or a cell mediated action, rather than to a specific modulation of cellular enzymes.     

Effects of dietary vitamin E and selenium on antioxidative defense mechanisms in the liver of rats treated with high doses of glucocorticoid

The aim of this work was to determine the effects of dietary intake vitamin E and selenium (Se) on lipid peroxidation as thiobarbituric acid reactive substances (TBARS) and on the antioxidative defense mechanisms in the liver of rats treated with high doses of prednisolone. Two hundred fifty adult male Wistar rats were randomly divided into five groups. The rats were fed a normal diet, but groups 3, 4, and 5 received a daily supplement in their drinking water of 20 mg vitamin E, 0.3 mg Se, and a combination of vitamin E and Se, respectively, for 30 d. For 3 d subsequently, the control group (group 1) was treated with a placebo, and the remaining four groups were injected intramuscularly with 100 mg/kg body weight (BW) prednisolone. After the last administration of prednisolone, 10 rats from each group were killed at 4, 8, 12, 24, and 48 h and the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) enzymes and the levels of glutathione (GSH) and TBARS in their livers were measured. GSH-Px, SOD, and CAT enzyme activities and GSH levels in prednisolone-treatment group (group 2) began to decrease gradually at 4 h, falling respectively to 38%, 55%, and 40% of the control levels by 24 h, and recovering to the control levels at 48 h. In contrast, prednisolone administration caused an increase in the hepatic TBARS, reaching up to four times the levels of the control at 24 h. However, supplementation with vitamin E and Se had a preventive effect on the elevation of the hepatic TBARS and improved the diminished activities of the antioxidative enzymes and the levels of GSH. Therefore, the present study demonstrates the effectiveness of vitamin E and Se in reducing hepatic damage in glucocorticoid-treated rats and suggests that reductions in increased TBARS as a result of prednisolone may be an important factor in the action of vitamin E and Se.     

Two cinnamate derivatives produce similar alteration in mRNA expression and activity of antioxidant enzymes in rats

Cinnamate is a widespread secondary metabolite of phenolic compound synthesized by plants for defensive purposes. The current study was designed to investigate the effect of two structurally related cinnamate derivatives, 4-hydroxycinnamate and 3-(4-hydroxyphenyl)propionic acid (HPP), on the mRNA expression and activity of antioxidant enzymes in high-cholesterol-fed rats. Male rats were fed a 1 g/100 g high-cholesterol diet with supplements of either 4-hydroxycinnamate or HPP (0.135 mmol/100 g diet) for 6 weeks. The plasma paraoxonase activity was found to be higher in the cinnamate-derivative-supplemented groups than in the control group. The erythrocyte superoxide dismutase (SOD) and catalase (CAT) activities, plus glutathione (GSH) level, were all significantly higher in the 4-hydroxycinnamate- and HPP-supplemented groups than in the control group. However, both 4-hydroxycinnamate and HPP supplementation significantly lowered the hepatic activities and mRNA expression of CAT and glutathione peroxidase (GSH-Px) compared to the control group. The hepatic mRNA expression and activity of SOD did not differ between the groups. The hepatic thiobarbituric acid reactive substances (TBARS) level was significantly lowered by the 4-hydroxycinnamate and HPP supplementation. Accordingly, these results indicate that supplementation by 4-hydroxycinnamate and HPP would seem to enhance the antioxidative defense of erythrocyte. Both HPP and 4-hydroxycinnamate would appear to be beneficial in improving the function of antioxidative enzymes on a molecular level in high-cholesterol-fed rats.     

Hypocholesterolemic and antioxidant properties of 3-(4-hydroxyl)propanoic acid derivatives in high-cholesterol fed rats

The purpose of the present study was to evaluate the in vivo efficacy of two cinnamic acid synthetic derivatives (allyl 3-[4-hydroxyphenyl]propanoate; HPP304, 1-naphthyl-methyl 3-[4-hydroxyphenyl]propanoate; HPP305) in high-cholesterol fed rats and compare their actions to that of cinnamic acid. Cinnamic acid and its synthetic derivatives were supplemented with a high-cholesterol diet for 42 days at a dose of 0.135 mmol/100 g of diet. The supplementation of HPP304 and HPP305 significantly lowered cholesterol and triglyceride levels in the plasma and liver with a simultaneous increase in the HDL-cholesterol concentration, whereas cinnamic acid only lowered the plasma cholesterol concentration. Cinnamic acid lowered hepatic HMG-CoA reductase activity in high-cholesterol fed rats, however, its synthetic derivatives (HPP304 and HPP305) did not affect HMG-CoA reductase activity compared to the control group. Instead, the HPP304 and HPP305 supplements significantly lowered hepatic acyl coenzyme A:cholesterol acyltransferase activity and increased the fecal bile acid. The SOD activity of the erythrocytes and liver was not different between the groups, however, the activities of CAT and GSH-Px, and the level of GSH in the erythrocytes were significantly higher in the HPP304 and HPP305 groups than in the control group. On the other hand, the activities of CAT and GSH-Px, and the level of malondialdehyde in the liver were significantly lower in the HPP304 and HPP305 groups. The antioxidant activities of these cinnamic acid synthetic derivatives were similar to the cinnamic acid in the high-cholesterol fed rats. In addition, HPP304 and HPP305 lowered amniotransferase activity in the plasma. These results suggest that two cinnamic acid synthetic derivatives (HPP304 and HPP305) exert lipid-lowering action and antioxidant properties without hepatotoxicity in high-cholesterol fed rats.     

Attenuating effect of chlorella supplementation on oxidative stress and NFkappaB activation in peritoneal macrophages and liver of C57BL/6 mice fed on an atherogenic diet

This study was designed to investigate whether chlorella supplementation may ameliorate oxidative stress and nuclear factor kappa B (NFkappaB) activation in peritoneal macrophages and liver of C57BL/6 mice fed on an atherogenic diet. The animals were maintained on an atherogenic diet (control), or an atherogenic diet supplemented with 3% (w/w) chlorella or 5% (w/w) chlorella for 12 wks. The plasma and hepatic lipid levels were not affected by chlorella supplementation. Hepatic thiobarbituric acid-reactive substances and superoxide anion production in peritoneal macrophages were significantly lower in the 5% chlorella group (p<0.05), but the glutathione level was not altered by chlorella supplementation. The hepatic antioxidative enzyme activities of Cu, Zn-superoxide dismutase and catalase were higher in the mice fed on the 5% chlorella diet (p<0.05). The plasma aspartate aminotransferase activity was lower in the mice fed on the chlorella-containing diets (p<0.05), whereas the alanine aminotransferase activity was not affected by chlorella supplementation. The NFkappaB nuclear binding activities of peritoneal macrophages and liver were significantly lower in the 5% chlorella groups (p<0.05). These results suggest that chlorella supplementation may attenuate oxidative stress by reducing reactive oxygen production and increasing antioxidative processes, thus suppressing inflammatory mediator activation in peritoneal macrophages and liver.     

Evaluation of hesperetin 7-O-lauryl ether as lipid-lowering agent in high-cholesterol-fed rats

The lipid-lowering efficacy of hesperetin was revealed in preliminary studies on experimental animals. As such, the current study compared the effect of hesperetin 7-O-lauryl ether, with that of hesperetin and lovastatin on the lipid profile and cholesterol-regulating mechanism in high-cholesterol-fed rats. Male rats were fed a high-cholesterol diet (1%, wt/wt) or high-cholesterol diet supplemented with lovastatin (1, 0.02%, wt/wt), hesperetin (2, 0.02%, wt/wt), or hesperetin 7-O-lauryl ether (3, 0.031%, wt/wt) for six weeks. The supplemental amount of 3 was 0.066mmol/100g diet as an equivalent to the supplemental amount of 2. The plasma total cholesterol and triglyceride levels were significantly lowered by the 2 and 3 supplements compared with the control or 1-supplemented group. The hepatic HMG-CoA reductase activities were also significantly lower in all the supplemented groups compared with the control group, and the hepatic ACAT activity was significantly lower in the 2- and 3-supplemented groups. The supplementation of 3 resulted in a higher excretion of total neutral sterol and total fecal sterol compared with the control or 1-supplemented group. Accordingly, overall, compound 3, exhibited a more potent plasma lipid-lowering effect than compound 1 based on inhibiting cholesterol biosynthesis and esterification, while also increasing the fecal sterol excretion.     

Cholesterol-rich diets have different effects on lipid peroxidation, cholesterol oxides, and antioxidant enzymes in rats and rabbits

The objective of this study was to compare the effect of cholesterol feeding of rats and rabbits. The levels of lipid peroxidation products and oxysterols in the plasma of the two species plus the antioxidant enzyme activities in the liver and erythrocytes were measured to explain their different susceptibilities to atherosclerosis. Our study showed that rats are less susceptible than are rabbits to the atherogenic effect of a cholesterol-rich diet because of differences in lipid peroxidation products as well as antioxidant enzymes activities in their livers. In rabbits, cholesterol feeding produced severe hypercholesterolemia (43-fold increase) and increased plasma and liver lipid peroxidation. Total as well as the individual oxysterol contents of 7alpha-, 7beta-hydroxycholesterol, alpha-epoxy, beta-epoxycholesterol, cholestanetriol, 7-keto, and 27-hydroxycholesterol significantly increased in the plasma of hypercholesterolemic (HC) rabbits. Erythrocyte glutathione peroxidase (GSH-Px) activity significantly decreased whereas catalase activity significantly increased in HC rabbits. In rats cholesterol feeding increased the plasma cholesterol only twofold and had no effect on plasma or liver lipid peroxidation. Only 7alpha- and 7beta-hydroxycholesterol increased and no change was observed in any of the antioxidant enzymes activity in the erythrocytes. Although cholesterol feeding caused a 10-fold increase of liver cholesterol as ester in both rats and rabbits, the antioxidant enzyme GSH-Px and catalase activities in the liver significantly increased in rats but significantly decreased in rabbits. The increase of GSH-Px and catalase activities in the liver of cholesterol fed rats could have a protective role against oxidation, thus preventing the formation of lipid peroxidation and oxysterols.     

Effect of red wine on oxidative stress and hypercholesterolemia induced by feeding a high-cholesterol diet in rat

The effect of red wine on oxidative stress and hypercholesterolemia induced by feeding a high-cholesterol diet (supplemented with 1.65% of cholesterol (w/w) for 4 weeks) to female Wistar rats was examined. When red wine was simultaneously supplemented to high-cholesterol diet, total cholesterol, triglycerides, atherogenic index and lipid peroxidation products significantly decreased compared with the high-cholesterol diet alone, while GSH content and antioxidative enzymes activities were enhanced. In the hypercholesterolemic rat the excretion of fecal bile acids, as well as their plasma and hepatic concentrations were increased significantly. Administration of red wine enhanced these values, indicating an increase in the cholesterol degradation. These results suggest that red wine may have a protective effect against oxidative stress, hypercholesterolemia and atherogenic index induced by high-cholesterol diet.     

Dietary vitamin C supplementation decreases blood pressure in DOCA-salt hypertensive male Sprague Dawley rats and this is associated with increased liver oxidative stress

The effects of a vitamin C supplemented diet on blood pressure, body and liver weights, liver antioxidant status, iron and copper levels were investigated in DOCA-salt treated and untreated Sprague-Dawley (SD) male rats after 8 weeks of treatment. Vitamin C supplementation had no effect on blood pressure in SD rats but induced a significant decrease in blood pressure in DOCA-salt treated rats, the decrease being more efficient at 50 mg/kg of vitamin C than at 500 mg/kg. Hepatic lipid peroxidation and iron levels were significantly increased in DOCA-salt hypertensive rats whereas total hepatic antioxidant capacity (HAC), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were decreased. Vitamin C supplementation did not affect the overall antioxidant defences of control SD rat livers. In contrast, vitamin C supplementation accentuated the DOCA-salt induced accumulation of liver iron and lipid peroxidation. This occurred without any notable aggravation in the antioxidant deficiency of vitamin C supplemented DOCA-salt treated rat livers. Our data suggest that DOCA-salt treatment induces an accumulation of iron in rat livers which is responsible for the prooxidant effect of vitamin C. The normalization of blood pressure in DOCA-salt treated rats by vitamin C supplementation appears thus independent from liver antioxidant status.     

The effects of some antioxidant vitamin- and trace element-supplemented diets on activities of SOD, CAT, GSH-Px and LPO levels in chicken tissues

The effect of diets containing antioxidant vitamins and trace elements on chicken tissue activities of SOD, CAT, GSH-Px and of LPO levels was investigated. Chickens, 45 weeks of age were divided into six groups: control group, Cu group (13.2 mg Cu kg(-1) diet); Se group (0.07 mg Se kg(-l) diet); vitamin E group (70 mg DL-alpha-tocopherol acetate kg(-1) diet) and a constant level vitamin C, 200 mg kg(-1) diet); vitamin A group (240 mg retinol acetate kg(-1) diet) and vitamin C group (500 mg ascorbic acid kg(-1) diet). Significant variation of these antioxidant enzyme activities and LPO levels according to gender was demonstrated statistically. In the Cu group, CuZnSOD activity in the liver, erythrocyte, kidney and heart significantly increased by 75, 40, 12, 12% respectively (P<0.05). MnSOD activity in the heart, liver, kidney and brain of the vitamin C and in the heart of Cu group were found to be increased by approximately 15%, while in liver tissue of the Cu group it was reduced by 19% (P<0.05). GSH-Px activities in the Se, vitamin E and C groups were significantly increased, conversely LPO levels decreased (P<0.001). CAT activities in the liver and heart of the vitamin C group were significantly decreased (by 32%), but in kidney tissue only that of the Cu group was increased from 30.2 +/- 4.767 to 144.49 +/- 6.93 U mg(-1) P<0.001. The resistance to stress of the vitamin E and C groups, which had significantly increased activities of antioxidant enzymes and decreased lipid peroxide levels, were determined in 60% moisture medium at 45 degrees C.     

Effects of the calcium channel blocker amlodipine on serum and aortic cholesterol,lipid peroxidation,antioxidant status and aortic histology in cholesterol-fed rabbits

Reactive oxygen metabolites and oxidized fatty acids are proinflammatory and are involved in the pathophysiology of atherosclerosis. Amlodipine, a unique third-generation dihydropyridine-type calcium channel blocker, seems to exert atheroprotective effects through its antioxidant properties related to its chemical structure and independent of its calcium channel-blocking effect. In this study, the interactions of amlodipine with major cellular antioxidants were investigated in order to elucidate the mechanisms underlying its atheroprotective effects. New Zealand white male rabbits were fed regular chow (group 1), chow with 1% cholesterol (group 2), regular chow plus 5 mg/kg/day amlodipine per os (group 3) and 1% cholesterol plus amlodipine (group 4) for 8 weeks. Total cholesterol, malondialdehyde (MDA) and vitamin E concentrations and catalase and superoxide dismutase (SOD) activities were determined in blood drawn before and after the experimental period. Aortic tissue was examined for atherosclerotic changes and aortic total cholesterol, MDA, catalase and SOD were determined. At the end of the 8-week treatment period, serum total cholesterol and plasma MDA were elevated in groups 2 and 4. In group 2, serum vitamin E and plasma SOD diminished (p < 0.05) and catalase increased (p < 0.05). In group 4, SOD activity increased at the end of treatment. MDA levels were lower and plasma SOD activities were higher in group 4 than in group 2. Aortic tissue investigations revealed higher total cholesterol and MDA concentrations and catalase activities in group 2 than in group 4, and the highest tissue SOD activity was recorded in group 4 (p < 0.05 for all comparisons). Morphological examination of aortic tissues exhibited endothelial disarrangement and lipid deposition in group 2. Histopathological alterations related to atherogenesis were less in group 4 than in group 2. Amlodipine seems to exert atheroprotective effects by reducing aortic cholesterol accumulation and blood and aortic lipid peroxidation, enhancing SOD activity both in blood and aortic tissue and suppressing the consumption of vitamin E. On the other hand, the suppression of catalase activity in blood and the aorta interferes with the drug's well-known antioxidant effects.