Vitamin C and E supplements improve the impaired antioxidant status and decrease plasma lipid peroxides in hemodialysis patients small star,filled

This study investigated the supplementation with vitamin C or/and E on the antioxidant system in hemodialysis patients. Thirty-eight hemodialysis patients (27 males and 11 females) with the average of 60 years old were divided into four groups: placebo (400 mg starch/time), vitamin C (400 mg/time)-, vitamin E (400 mg d,l- alpha-tocopheryl acetate/time)-, and vitamin C (400 mg/time) + E (400 mg d,l- alpha-tocopheryl acetate/time)-supplemented groups for 6-week supplementation. The patients orally received three capsules of placebo or antioxidant(s) three times a week after finishing hemodialysis. Thirty-six healthy subjects (22 males and 14 females) with the average of 58 years old were recruited as the control group. Hemodialysis patients significantly decreased plasma vitamin C by 32%, erythrocyte glutathione by 26%, and plasma total antioxidant status by 9%, but increased plasma lipid peroxide levels by 102% compared with the control group at the baseline. The levels of plasma vitamin C and total antioxidant status significantly decreased by 24% and 18%, respectively, from the post-dialysate compared with those from the pre-dialysate. At week 6, vitamin C + E-supplemented group significantly increased plasma vitamin C and E, erythrocyte glutathione, and plasma antioxidant status, and inhibited plasma lipid peroxides compared with placebo group. Additionally, vitamin C + E-supplemented group had higher plasma vitamin C, vitamin E, and total antioxidant status, and lower plasma lipid peroxides than placebo group even at least 2 weeks after the termination of the supplements. Therefore, antioxidant vitamin supplements could improve antioxidant status and decrease lipid peroxides of hemodialysis patients.     

Effects of beta-carotene and alpha-tocopherol on radical-initiated peroxidation of microsomes.

Rat liver microsomal membranes were exposed to either beta-nicotinamide adenine dinucleotide phosphate (NADPH), adenosine 5'-diphosphate (ADP), and Fe+3 or to azocompounds, and the antioxidant activities of beta-carotene and alpha-tocopherol were studied. Lipid peroxidation was monitored either by malondialdehyde (MDA) formation in the thiobarbituric acid assay at 535 nm or by hydroperoxide formation at 234 nm, after high-pressure liquid chromatography (HPLC) separation of phospholipid hydroperoxides. The radical initiators, water-soluble 2,2'-azobis(2-amidinopropane) (AAPH) and lipid-soluble 2,2'-azobis(2,4-dimethylvaleronitrile (AMVN), when thermally decomposed at 37 degrees C under air, produced a constant rate of lipid peroxidation in microsomes and lag times inversely related to their concentrations. Using 25 mM AAPH, beta-carotene suppressed lipid peroxidation at a concentration of 50 nmol/mg protein; using 24 mM AMVN, an inhibition of MDA formation was observed at a concentration of only 5 nmol/mg protein. Inhibition by beta-carotene did not produce a clearly defined lag phase. During AAPH-induced lipid peroxidation, beta-carotene was consumed linearly, and high levels of the antioxidant were still present at the end of 45 min of incubation. Using NADPH/ADP/Fe+3, protection by beta-carotene was observed at 10 nmol/mg protein. alpha-Tocopherol effectively suppressed both MDA and hydroperoxide formation in a dose-dependent manner when either NADPH/ADP/Fe+3 or azocompounds were used. These effects were observed at very low concentrations of the added alpha-tocopherol, ranging from 2 to 3 nmol/mg protein. When the lag times were measurable (AAPH and AMVN), they were directly proportional to the concentration of alpha-tocopherol and revealed the presence of endogenous antioxidants in the microsomal membranes. Different temporal relationships between the loss of alpha-tocopherol and lipid peroxidation were observed in relation to the prooxidant used. A substantial depletion of about 70% of endogenous alpha-tocopherol preceded the propagation phase when induced by the azocompounds, while only 20% of antioxidant disappeared at the beginning of the peroxidation when induced by NADPH/ADP/Fe+3. Although our results show that both beta-carotene and alpha-tocopherol suppress the peroxidation of microsomal membranes, their antioxidant efficacy is influenced by several factors, including the type of radical initiator involved and the site and rate of radical production.     

Hypolipidemic and antioxidative effects of the plant glycoprotein (36 kDa) from Rhus verniciflua stokes fruit in Triton WR-1339-induced hyperlipidemic mice

We investigated the hypolipidemic and antioxidative effects on male ICR mice of a glycoprotein isolated from Rhus verniciflua Stokes (RVS) fruit. The administration of the RVS glycoprotein (100 mg/kg) for two weeks resulted in a significant decrease in such plasma lipid levels as total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL). The levels of TC, TG and LDL in the hyperlipidemic model were significantly increased, whereas the high-density lipoprotein (HDL) level was considerably decreased. The 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity and the level of thiobarbituric acid-reactive substances (TBARS) were significantly elevated, whereas the production of nitric oxide (NO) was diminished. Moreover, the administration of the RVS glycoprotein prior to inducing hyperlipidemic mice suppressed the increase in the plasma lipid levels (TC, TG and LDL), and decrease in the HDL level in Triton WR-1339-induced hyperlipidemic mice. Furthermore, the RVS glycoprotein significantly inhibited the activity of HMG-CoA reductase and the levels of TBARS in the hyperlipidemic mice. In addition, the activities of detoxicant enzymes [catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)] were gradually augmented after a supplement with the RVS glycoprotein. The results suggest that the RVS glycoprotein would be effective in preventing an increase in the plasma lipid levels and in improving the antioxidant levels. This protein might be useful as a therapeutic agent.     

Efficacy of piperine, an alkaloidal constituent from Piper nigrum on erythrocyte antioxidant status in high fat diet and antithyroid drug induced hyperlipidemic rats

The main aim of this study was to investigate the effect of piperine on erythrocyte antioxidant status in high fat diet (HFD) and antithyroid drug induced hyperlipidemic rats. Male Wistar rats were divided into eight groups. The first four groups were fed a control diet and in addition were given respectively 1% carboxymethyl cellulose (CMC); 10 mg/kg body weight carbimazole (CM); 10 mg CM + 40 mg/kg body weight piperine and 10 mg CM + 2 mg/kg body weight atorvastatin (ATV). A similar pattern was followed for the next four groups except that they were all fed HFD instead of the control diet. Erythrocyte osmotic fragility, total cholesterol, phospholipids, lipid peroxidation products, enzymic and non-enzymic antioxidant status were studied in all experimental groups. Significantly increased osmotic fragility, total cholesterol/phospholipid ratio, thiobarbituric acid reactive substances and lipid hydroperoxides were observed in the plasma and erythrocytes of HFD fed and CM treated rats compared to the control. Superoxide dismutase, catalase, glutathione peroxidase, vitamin E and reduced glutathione in erythrocytes and vitamin C in the plasma were also significantly lowered in HFD fed, antithyroid drug treated rats compared to control animals. Concurrent piperine supplementation along with HFD and antithyroid drug administration normalized erythrocyte osmotic fragility, reduced lipid peroxidation, and improved the enzymic and non-enzymic antioxidant status compared to those rats that did not receive piperine. Thus, our results indicate that piperine supplementation markedly protects erythrocytes from oxidative stress by improving the antioxidant status in HFD fed antithyroid drug treated rats.     

Effect of Indigofera tinctoria Linn on liver antioxidant defense system during D-galactosamine/endotoxin-induced acute hepatitis in rodents

Effects of pre-treatment with the alcoholic extract of I. tinctoria (500 mg/kg body wt/day, p.o. for 21 days) on liver antioxidant defense system during acute hepatitis induced by D-galactosamine (D-GalN)/endotoxin (LPS extracted by phenol water method from E. coli serotype 0111.B4; 300 mg and 30 micrograms/kg body wt/day, i.p., 18 hr before the assay) were investigated on the activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase and glutathione-s-transferase, and levels of total reduced glutathione in the liver of normal and experimental groups of male albino rats. Since lipid peroxidation and associated membrane damage is a key feature of D-galN/LPS-induced liver injury, the levels of lipid peroxides, was estimated and used as an index of oxidative stress. D-GalN/endotoxin-induced hepatic damage was manifested by a significant decrease in the activities of antioxidant enzymes, decreased glutathione levels and increased levels of lipid peroxides. I. tinctoria pre-treated rats showed considerable protection against D-galN/endotoxin, induced oxidative stress as evidenced by a significant increase in the activities of all the antioxidant enzymes studied and significant decrease in the levels of lipid peroxides. Results indicate that pretreatment with I. tinctoria extract in rats is very effective in reducing D-GalN/endotoxin-induced oxidative stress suggesting an antioxidant effect.     

Possible neuroprotective effects of lecithin and alpha-tocopherol alone or in combination against ischemia/reperfusion insult in rat brain

A close correlation exists between ischemia/reperfusion (I/R)-induced insult and the release of free radicals. Lecithin is a polyunsaturated phosphatidylcholine that corresponds to the phosphatidylcholine molecule. Phosphatidylcholines are high-energy functional and structural elements of all biologic membranes. alpha-Tocopherol is the major lipid-soluble chain-breaking antioxidant in the body tissues and effectively protects against neuronal damage. Therefore, we studied the effect of lecithin (300 mg/kg, p.o., 14 days) and alpha-tocopherol (200 mg/kg, p.o., 14 days), alone or in combination, on the brain redox state during I/R. Adult male Wistar rats were subjected to global ischemia by the occlusion of the two carotid arteries 24 h after the last dose of drug administration. Reperfusion was carried out 1 h after induction of ischemia and lasted for another hour. Brain lipid peroxides (MDA) and glutathione (GSH) contents, as well as superoxide dismutase (SOD) and catalase (CAT) activities were assessed. The results showed that I/R elevated brain lipid peroxides content which was accompanied by a reduction in both antioxidant enzyme activities, however, brain GSH level remained unaltered. Lecithin, alpha-tocopherol and their combination restored MDA content, as well as CAT activity with a slight tendency to normalize SOD activity. We conclude that lecithin has a possible neuroprotective effect partly through its antioxidant action which is comparable to that of alpha-tocopherol.     

Antioxidant effect of simvastatin is not enhanced by its association with alpha-tocopherol in hypercholesterolemic patients

Among the pleiotropic effects of statins, their antioxidant action may be involved in their protective effects. Thus, we investigated the antioxidant effect of simvastatin, associated or not with alpha-tocopherol, on levels of electronegative low-density lipoprotein (LDL-), nitrotyrosine, thiols (homocysteine, glutathione, cysteine, methionine), and lipid-soluble antioxidants in blood plasma of hypercholesterolemic subjects. In this study, 25 hypercholesterolemic subjects were treated for 2 months with simvastatin (20 mg/day) and with simvastatin (20 mg/day) + alpha-tocopherol (400 IU/day). Concentrations of thiols were determined by high-performance capillary electrophoresis-laser-induced fluorescene. Lipid-soluble antioxidants were determined by HPLC, and LDL-, and nitrotyrosine by ELISA. Simvastatin, independent of its association with alpha-tocopherol, reduced plasma concentrations of LDL-, nitrotyrosine, total cholesterol, and LDL cholesterol and the LDL cholesterol/HDL cholesterol ratio. Neither simvastatin nor simvastatin plus alpha-tocopherol altered plasma levels of the thiols analyzed. alpha-Tocopherol did not change the antioxidant effect of simvastatin on the levels of LDL- and nitrotyrosine in hypercholesterolemic subjects. The reduction of LDL- and nitrotyrosine by simvastatin seems to be related to the pleiotropic effects of this statin, and it may have an important protective effect against endothelial dysfunction and atherosclerosis.     

Chemopreventive potential of luteolin during colon carcinogenesis induced by 1,2-dimethylhydrazine

We investigated the chemopreventive potential of luteolin on hepatic and circulatory lipid peroxidation and antioxidant status during 1,2-dimethylhydrazine induced colon carcinogenesis in rats. Rats were given a weekly subcutaneous injection of DMH at a dose of 20 mg/kg body weight for 15 weeks. Luteolin (0.2 mg/kg body weight/everyday p.o.) was given at the initiation and also at the postinitiation stages of carcinogenesis to DMH treated rats. The animals were sacrificed at the end of 30 weeks. Enhanced lipid peroxidation in the liver and circulation of tumor bearing rats was accompanied by a significant decrease in the levels of plasma and hepatic reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), vitamin C, vitamin E and beta-carotene in DMH treated rats as compared to the control rats. Intragastric administration of luteolin (0.2mg/kg body weight) to DMH-treated rats significantly reduced the incidence and size of tumor in the colon, reduced lipid peroxidation levels and enhanced the plasma and hepatic activities of GSH, GPx, GST, GR, SOD, CAT, vitamin C, vitamin E and beta-carotene. Thus the chemopreventive efficacy of luteolin against colon carcinogenesis is evidenced by our preliminary studies which showed decreased incidence of tumors and the antiperoxidative and antioxidant effect of luteolin. Further study on the exact mechanism of action of luteolin in preventing colon carcinogenesis is yet to be elucidated.     

Veratric acid ameliorates hyperlipidemia and oxidative stress in Wistar rats fed an atherogenic diet

An investigation was made to reveal the protective effects of veratric acid (VA), a phenolic acid against atherogenic diet-induced hyperlipidemic rats. Male albino Wistar rats were fed with atherogenic diet (4% cholesterol, 1% cholic acid, and 0.5% 2-thiouracil) daily for 30 days and treated with VA (40 mg/kg body weight) daily for a period of 30 days. Rats fed with atherogenic diet showed significant (P < 0.05) elevation in the level of plasma lipids, systolic and diastolic blood pressure, oxidative stress markers (thiobarbituric acid reactive substances, lipid peroxides) and significant (P < 0.05) reduction in the activities of enzymatic (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic (vitamin C, vitamin E, and reduced glutathione) antioxidants in erythrocytes, plasma, and tissues (liver, kidney, and aorta). Oral administration of VA (40 mg/kg body weight) for 30 days to atherogenic diet fed rats markedly attenuates systolic, diastolic blood pressure and lipid peroxidation products. Further, VA treatment significantly improved enzymatic and non-enzymatic antioxidants levels and showed beneficial effects on lipid profile in atherogenic diet rats. All the above alterations were supported by histopathological observations. These results indicate that oral administration of VA ameliorates atherogenic diet-induced hyperlipidemia in rats by its free radical scavenging; improving the antioxidants and lipid lowering properties.     

Cyclosporine A induced changes to plasma and erythrocyte antioxidant defences

Organ transplant recipients develop pronounced cardiovascular disease, and decreased antioxidant capacity in plasma and erythrocytes is associated with the pathogenesis of this disease. These experiments tested the hypothesis that the immunosuppressant cyclosporine A (CsA) alters erythrocyte redox balance and reduces plasma antioxidant capacity. Female Sprague-Dawley rats were randomly assigned to a control or CsA treated group. Treatment animals received 25 mg/kg/day of CsA via intraperitoneal injection for 18 days. Control rats were injected with the same volume of the vehicle. Three hours after the final CsA injection, rats were exsanguinated and plasma analysed for total antioxidant status (TAS), alpha-tocopherol, malondialdehyde (MDA), and creatinine. Erythrocytes were analysed for superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glucose-6-phosphate dehydrogenase (G6PD) activities, alpha-tocopherol, and MDA. CsA administration resulted in a significant (P < 0.05) decrease in plasma TAS and significant increases (P < 0.05) in plasma creatinine and MDA. Erythrocyte CAT was significantly (P < 0.05) increased in CsA treated rats compared to controls. There were no significant differences (P > 0.05) in erythrocyte SOD, GPX, G6PD, alpha-tocopherol or MDA between groups. In summary, CsA alters erythrocyte antioxidant defence and decreases plasma total antioxidant capacity.     

Oral alpha-tocopherol supplementation inhibits lipid oxidation in established human atherosclerotic lesions

BACKGROUND: Much experimental evidence suggests that lipid oxidation is important in atherogenesis and in epidemiological studies dietary antioxidants appear protective against cardiovascular events. However, most large clinical trials failed to demonstrate benefit of oral antioxidant vitamin supplementation in high-risk subjects. This paradox questions whether ingestion of antioxidant vitamins significantly affects lipid oxidation within established atherosclerotic lesions. METHODS AND RESULTS: This placebo-controlled, double blind study of 104 carotid endarterectomy patients determined the effects of short-term alpha-tocopherol supplementation (500 IU/day) on lipid oxidation in plasma and advanced atherosclerotic lesions. In the 53 patients who received alpha-tocopherol there was a significant increase in plasma alpha-tocopherol concentrations (from 32.66 +/- 13.11 at baseline to 38.31 +/- 13.87 (mean +/- SD) micromol/l, p < 0.01), a 40% increase (compared with placebo patients) in circulating LDL-associated alpha-tocopherol (p < 0.0001), and their LDL was less susceptible to ex vivo oxidation than that of the placebo group (lag phase 115.3 +/- 28.2 and 104.4 +/- 15.7 min respectively, p < 0.02). Although the mean cholesterol-standardised alpha-tocopherol concentration within lesions did not increase, alpha-tocopherol concentrations in lesions correlated significantly with those in plasma, suggesting that plasma alpha-tocopherol levels can influence lesion levels. There was a significant inverse correlation in lesions between cholesterol-standardised levels of alpha-tocopherol and 7beta-hydroxycholesterol, a free radical oxidation product of cholesterol. CONCLUSIONS: These results suggest that within plasma and lesions alpha-tocopherol can act as an antioxidant. They may also explain why studies using < 500 IU alpha-tocopherol/day failed to demonstrate benefit of antioxidant therapy. Better understanding of the pharmacodynamics of oral antioxidants is required to guide future clinical trials.     

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.     

Plasma and erythrocytes antioxidant status and trace element levels in proteinuric patients with moderate glomerular function.

The objective of the study was to investigate the effect of moderate glomerular dysfunction on oxidative stress. We determined the plasma and erythrocyte malondialdehyde (MDA) levels, as a marker of lipid peroxidation, erythrocyte glutathione (GSH) levels and activities of GSH-Px, GSH Red and SOD as an antioxidant enzymes, and plasma trace element levels containing Fe, Cu and Zn in twenty proteinuric patients (6.8 +/- 5.1 g/day) with moderate glomerular function and in 20 anemic control subjects. We found that the erythrocyte and plasma MDA levels and erythrocyte GSH-Px activities were significantly higher (p < 0.001, p < 0.001, p < 0.001, respectively) and the erythrocyte GSH levels and activities of GSH-Red and SOD activities were significantly lower (p < 0.001, p < 0.001, p < 0.001, respectively) in the patients than in the anemic subjects. Plasma Fe and Zn levels were not to be found significantly different in the patients compared to the anemic subjects. But plasma Cu levels were significantly higher in the patients (p < 0.05) when compared with the levels of anemic subjects. This study was concluded that cellular antioxidant activity decreases in proteinuric patients with moderate glomerular function. This may increase lipid peroxidation reactions by causing oxidative stress in erythrocyte membranes.     

Exposure to the fern Onychium contiguum causes increase in lipid peroxidation and alters antioxidant status in urinary bladder

The status of lipid peroxidation, glutathione, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, superoxide dismutase, catalase, ascorbic acid, and alpha-tocopherol was studied in the urinary bladder of guinea pigs exposed to the carcinogenic fern Onychium contiguum. There was significant increase in the preformed lipid peroxides in the urinary bladders from fern exposed animals. The amount of lipid peroxides produced on incubation of urinary bladder homogenates with or without catalyst was significantly higher in the fern exposed animals. The concentrations of glutathione and alpha-tocopherol and the activities of glutathione reductase and catalase were elevated in the urinary bladders of the animals exposed to the fern. No effect was observed on the concentration of ascorbic acid and the activities of glutathione peroxidase, glutathione-S-transferase, and superoxide dismutase. It is summarized that the fern toxins increased oxidative stress in the urinary bladder and antioxidant status was altered. However, the altered antioxidant status did not provide protection from the toxin induced injury. Histopathology of the urinary bladder in the fern exposed animals revealed oedema, haemorrhages, and congestion. This is the first study to show increase in lipid peroxidation along with altered antioxidant status in the urinary bladder of fern exposed animals.     

Interrelationship of antioxidative status, lipid peroxidation, and lipid profile in insulin-dependent and non-insulin-dependent diabetic patients

This study aimed to investigate the interrelationship of plasma lipid profile, lipid peroxidation, and erythrocyte antioxidative defense in patients with insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. Plasma levels of total cholesterol, triglycerides, and lipid peroxides and the activities of copper, zinc superoxide dismutase (CuZnSOD), catalase, glutathione peroxidase (GSH-Px), as well as the amount of glutathione in erythrocytes, were determined in IDDM, NIDDM, and nondiabetic control subjects. Additionally, morphology of erythrocytes in all subjects was examined. Plasma levels of total cholesterol and triglycerides were significantly increased in NIDDM compared with controls. Also, the lipid peroxide level was higher in NIDDM than in either control or IDDM subjects. CuZnSOD activity in erythrocytes was elevated in NIDDM patients compared with the control. In NIDDM patients, more extensive erythrocyte spherocytosis and echinocytosis compared with both control and IDDM subjects were observed. In contrast with the IDDM group, the observed abnormality in lipid metabolism in NIDDM patients is closely associated with increased lipid peroxidation, changes in antioxidative defense, and erythrocyte morphology.     

Physical activity alters antioxidant status in exercising elderly subjects

Nutritional adequacy and physical activity are two aspects of a health-promoting lifestyle. Not much is known about antioxidant nutrient requirements for exercising elderly (EE) subjects. The question of whether exercise training alters the status of antioxidant vitamins as well as trace elements in elderly subjects and fails to balance the age-related increase in oxidative stress is addressed in this study. There were 18 EE (68.1+/-3.1 years), 7 sedentary elderly (SE; 70.4+/-5.0 years), 17 exercising young (EY; 31.2+/-7.1 years) and 8 sedentary young (SY; 27.1+/-5.8 years) subjects who completed 7-day food and activity records. Each subject's blood was sampled on Day 8. A similar selenium (Se) status but a higher erythrocyte glutathione peroxidase (GSH-Px) activity were found in EE subjects as compared with EY and SE subjects. Blood oxidized glutathione was higher and plasma total thiol was lower in EE subjects as compared with EY subjects. Mean vitamin C (167 vs. 106 mg/day), vitamin E (11.7 vs. 8.3 mg/day) and beta-carotene (4 vs. 2.4 mg/day) intakes were higher in EE subjects as compared with EY subjects. However, EE subjects exhibited the lowest plasma carotenoid concentrations, especially in beta-carotene, which was not related to intakes. Despite high intakes of antioxidant micronutrients, no adaptive mechanism able to counteract the increased oxidative stress in aging was found in EE subjects. Results on GSH-Px activity illustrate that the nature of the regulation of this biomarker of Se status is different in response to training and aging. These data also strongly suggest specific antioxidant requirements for athletes with advancing age, with a special attention to carotenoids.     

No evidence for oxidative stress as a mechanism of action of hyperhomocysteinemia in humans

Oxidative stress has been suggested as one of the physiopathologic conditions underlying the association of total plasma homocysteine (p-tHcy) with cardiovascular disease (CVD), but this hypothesis has not been validated in human epidemiological studies. We measured plasma and erythrocyte antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD), along with serum lipid-soluble antioxidants alpha-tocopherol, beta-carotene, lycopene and retinol, in a sample of 123 healthy elderly subjects (54 men, 69 women). Plasma malondialdehyde (p-MDA) was determined as a marker of lipid peroxidation, and p-tHcy was quantified by HPLC. No significant differences were found for p-MDA, GPx or SOD activities or serum antioxidant concentrations, in subjects with elevated p-tHcy (≥15 μmol/l) as compared to those with lower plasma homocysteine. Hyperhomocysteinemia did not lead to increased risk of having the highest p-MDA values, in either sex. We found no evidence that p-tHcy was associated with lipid peroxidation in this elderly human sample. Our results do not support the view that hyperhomocysteinemia would induce an adaptive response of antioxidant systems, either. More epidemiologic and clinical research is needed to clarify whether homocysteine promotes atherosclerosis by means of an oxidative stress mechanism.     

Aldehyde and Xanthine Oxidase Activities in Tissues of Streptozotocin-Induced Diabetic Rats: Effects of Vitamin E and Selenium Supplementation

Effects of vitamin E and selenium supplementation on aldehyde oxidase (AO) and xanthine oxidase (XO) activities and antioxidant status in liver, kidney, and heart of streptozotocin (STZ)-induced diabetic rats were examined. AO and XO activities increased significantly after induction of diabetes in rats. Following oral vitamin E (300 mg/kg) and sodium selenite (0.5 mg/kg) intake once a day for 4 weeks, XO activity decreased significantly. AO activity decreased significantly in liver, but remained unchanged in kidney and heart of vitamin E- and selenium-treated rats compared to the diabetic rats. Total antioxidants status, paraoxonase-1 (PON1) and erythrocyte superoxide dismutase activities significantly decreased in the diabetic rats compared to the controls, while a higher fasting plasma glucose level was observed in the diabetic animals. The glutathione peroxidase activity remained statistically unchanged. Malondialdehyde and oxidized low-density lipoprotein levels were higher in the diabetic animals; however, these values were significantly reduced following vitamin E and selenium supplementation. In summary, both AO and XO activities increase in STZ-induced diabetic rats, and vitamin E and selenium supplementation can reduce these activities. The results also indicate that administration of vitamin E and selenium has hypolipidemic, hypoglycemic, and antioxidative effects. It decreases tissue damages in diabetic rats, too.     

Lipid peroxidation, antioxidant status and survival in institutionalised elderly: a five-year longitudinal study

Oxidative stress has been related to ageing and risk of death. To determine whether oxidative status was associated with all-cause risk of death we carried out a prospective study in 154 non-smoking Spanish elderly without major illness. Baseline glutathione peroxidase (GPx) and superoxide dismutase (SOD) were analysed in plasma and erythrocytes. alpha-tocopherol, beta-carotene, lycopene and retinol were determined in serum samples and malondialdehyde (MDA), as a lipid peroxidation marker, in plasma. Mean survival time was 4.3 years. A total of 31 death cases (20.1%) occurred during the follow-up. Plasma-MDA predicted mortality independently of all other variables, while erythrocyte-SOD (e-SOD), beta-carotene and alpha-tocopherol were positively associated with survival. alpha-tocopherol and MDA were revealed as independent predictors in a joint survival model, being the group with low MDA and high alpha-tocopherol that with the lowest mortality. In conclusion, a higher risk of death was associated with increased lipid peroxidation and lower antioxidant defenses.     

箬叶多糖及其化学修饰物、亚硒酸钠和GSH对Cu~(2+)诱导的LDL氧化修饰的保护作用

研究了箬叶多糖ＦⅢ－ａ及其化学修饰物、亚硒酸钠和ＧＳＨ对Ｃｕ２＋诱导的低密度脂蛋白氧化修饰的保护作用．其结果表明箬叶多糖、硫酸酯多糖、硒酸酯多糖可显著抑制脂质过氧化产物（ＴＢＡＲＳ）及荧光物质的生成,彼此之间无明显差异．但对ＶＥ的消耗有着不同的保护作用,其顺序是ＦⅢ－ａ＞Ｓ－ＦⅢ－ａ＞Ｓｅ－ＦⅢ－ａ,并且具有明显的量效关系．硒或ＧＳＨ对Ｃｕ２＋诱导的ＬＤＬ氧化修饰无明显的抑制,但联合使用在０．１２５ｍｍｏｌ／ＬＮａ２ＳｅＯ３和０．２ｍｍｏｌ／ＬＧＳＨ及１２．５μｍｏｌ／ＬＮａ２ＳｅＯ３和０．０２ｍｍｏｌ／ＬＧＳＨ的浓度下能强烈地抑制ＴＢＡＲＳ的生成,甚至比正常的ＬＤＬ还要低．但是对ＶＥ的消耗只有较弱的保护作用,硒酸酯多糖与此相似．Ｎａ２ＳｅＯ３在０．１２５ｍｍｏｌ／Ｌ时可以明显抑制荧光物质的生成．