Lipid peroxidation and glutathione system in hyperlipemic rabbits: influence of olive oil administration

We studied the effect of supplementation (10% w/w) of a hyperlipemic diet (1% cholesterol) with olive oil (OLIV) for 6 weeks in four groups of 10 rabbits each. At the end of this period, we determined lipid peroxidation, glutathione content, and glutathione peroxidase, reductase and transferase activities in liver, brain, heart, aorta and platelets. The atherogenic diet increased tissue lipid peroxidation and decreased the protective antioxidant effect of glutathione. Dietary supplementation with olive oil reduced tissue lipid peroxidation by 71.6% in liver, 20.3% in brain, 84.5% in heart, 63.6% in aorta, 72% in platelets. The ratios total/oxidized glutathione were increased in all tissues (49% in liver, 48% in brain, 45% in heart, 83% in aorta, 70% in platelets). Olive oil increased glutathione peroxidase and transferase activities in all tissues. We conclude that in rabbits made hyperlipemic with a diet rich in saturated fatty acids, olive oil decreased tissue oxidative stress.     

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.     

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.     

Protective effect of N-acetylcysteine in isoniazid induced hepatic injury in growing rats

Status of oxidative/antioxidative profile was the mechanistic approach to inumerate the nature of protection by N-acetylcysteine (NAC) in isoniazid (INH) exposed experimental animals. Analysis of lipid peroxidation, thiol levels, cytochrome P450, superoxide dismutase (SOD), catalase, glutathione peroxidase, reductase and transferase were estimated in liver along with the body and liver weight of animals and histological observations. Isoniazid exposure to animals resulted in no change in body and liver weights. Thiols, lipid peroxidation, catalase, SOD glutathione peroxidase, reductase, transferase and cytochrome P450 levels were altered with INH exposure. Supplementation of NAC with INH protected the animals against hepatotoxic reactions by minimizing the free radical induced tissue injury and overall maintenance of the endogenous scavengers of free radicals.     

Effects of selenium-deficient diets on the production of prostaglandins and other oxygenated metabolites of arachidonic acid and linoleic acid by rat and rabbit aortae

Selenium is an essential component of glutathione peroxidase, which reduces free and esterified hydroperoxides of polyunsaturated fatty acids. Adequate glutathione peroxidase activity could be important for the maintenance of prostacyclin synthesis by blood vessels, since hydroperoxides can inhibit the formation of this substance. We have investigated the effects of dietary selenium deficiency on glutathione peroxidase activity and the synthesis of 6-oxoprostaglandin F1 alpha and monohydroxy and trihydroxy metabolites of polyunsaturated fatty acids by aorta. The latter products can be formed either by the actions of cyclooxygenase or lipoxygenase or by lipid peroxidation. Aortic glutathione peroxidase activity was reduced by over 80% by feeding rats a selenium-deficient diet for 4 weeks, and to undetectable levels after 6 weeks. There were no appreciable differences in the levels of free and esterified oxygenated metabolites of linoleic acid or arachidonic acid between the control and treated groups after 4 weeks. However, after 6 weeks, there were modest, but statistically significant reductions in the formation of 6-oxoprostaglandin F1 alpha and monohydroxy products formed by cyclooxygenase. On the other hand, the amounts of esterified 18:2 metabolites appeared to be higher in aortae from animals on the selenium-deficient diet, although only the increase in esterified 9-hydroxy-10,12-octadecadienoic acid was statistically significant. These results suggest that selenium deficiency can affect the formation of prostacyclin and other oxygenated metabolites of polyunsaturated fatty acids by aorta, possibly by increasing lipid peroxidation. However, the differences between control and selenium-deficient rats after 6 weeks were not very dramatic, in spite of the fact that glutathione peroxidase activity was undetectable. It would therefore appear that additional mechanisms are also involved in controlling the levels of lipid hydroperoxides in aorta.     

Effect of Garlic Supplementation on Erythrocytes Antioxidant Parameters, Lipid Peroxidation, and Atherosclerotic Plaque Formation Process in Oxidized Oil-Fed Rabbits

Effect of garlic supplementation on blood antioxidant status, lipid peroxidation, and coronary plaque formation process was investigated in oxidized oil-fed rabbits. Eighteen adult male mixed European rabbits were given a balanced diet (21 g% protein, 34 g% fat, 45 g% carbohydrate), which contained isocaloristic addition of nonoxidized or oxidized rapeseed oil in the presence and absence of garlic. The experiment lasted 24 weeks. At the beginning and every 6 weeks, rabbits were weighed, and blood was taken. To evaluate the antioxidant status of the rabbits, erythrocytes malondialdehyde (MDA) concentration, total superoxide dismutase (t-SOD), and glutathione peroxidase (GPX) activations were determined. After the experiment was completed, aortas were dissected for histological examinations. Changes in the contents of the above parameters and histological examinations showed that oxidized rapeseed, oil administered to rabbits, caused the development of atherosclerotic changes and disturbed antioxidant status. The addition of garlic in such diets inhibited atherosclerotic changes in the aorta wall, and it is related to the homeostatic activity of antioxidative enzymes and lipid peroxidation.     

Protective effect of green tea against lipid peroxidation in the rat liver, blood serum and the brain

This paper reports data on the effect of green tea on the lipid peroxidation products formation and parameters of antioxidative system of the liver, blood serum and central nervous tissue of healthy young rats drinking green tea for five weeks. The rats were permitted free access to solubilized extract of green tea. Bioactive ingredients of green tea extract caused in the liver an increase in the activity of glutathione peroxidase and glutathione reductase and in the content of reduced glutathione as well as marked decrease in lipid hydroperoxides (LOOH), 4-hydroksynonenal (4-HNE) and malondialdehyde (MDA). The concentration of vitamin A increased by about 40%. Minor changes in the measured parameters were observed in the blood serum. GSH content increased slightly, whereas the index of the total antioxidant status increased significantly. In contrast, the lipid peroxidation products, particularly MDA was significantly diminished. In the central nervous tissue the activity of superoxide dismutase and glutathione peroxidase decreased while the activity od glutathione reductase and catalase increased after drinking green tea. Moreover the level of LOOH, 4-HNE and MDA significantly decreased. The use of green tea extract appeared to be beneficial to rats in reducing lipid peroxidation products. These results support and substantiate traditional consumption of green tea as protection against lipid peroxidation in the liver, blood serum, and central nervous tissue.     

Suppression of fatty acid synthase by dietary polyunsaturated fatty acids is mediated by fat itself,not by peroxidative mechanism

This study examined the effect of dietary polyunsaturated fatty acids (PUFA) that were supplemented with vitamin E on lipid peroxidation, glutathione-dependent detoxifying enzyme system activity, and lipogenic fatty acid synthase (FAS) expression in rat liver. Male Sprague-Dawley rats were fed semipurified diets containing either 1% (w/w) corn oil or 10% each of beef tallow, corn oil, perilla oil, and fish oil for 4 wk. Alpha-tocopherol was supplemented in perilla oil (0.015%) and fish oil (0.019%). Hepatic thiobarbituric acid reactive substances, an estimate of lipid peroxidation, were not significantly different among the dietary groups. The glutathione peroxidase, glutathione reductase, and glutathione S-transferase activities were all elevated by the polyunsaturated fats, especially fish oil. The activity of FAS was reduced in the polyunsaturated fat-fed groups in the order of fish oil, perilla oil, and corn oil. The mRNA contents decreased in rats that were fed the 10% fat diets, particularly polyunsaturated fats, compared with the rats that were fed the 1% corn oil diet. Similarly, the inhibitory effect was the greatest in fish oil. These results suggest that lipid peroxidation can be minimized by vitamin E; PUFA in itself has a suppressive effect on lipogenic enzyme.     

Regional distribution of glutathione-related antioxidant defences in the normal rabbit aorta

In 6 normal rabbits, the aortic arch, the descending thoracic and the abdominal aorta were tested for non proteic thiol compounds, selenium-dependent and selenium-independent glutatione peroxidase, glutatione reductase, glutatione transferase and thiobarbituric acid reactive substances. The aortic arch showed the greatest content of non proteic thiol compounds and thiobarbituric acid reactive substances, associated to the highest activities of glutathione-related enzymes. However, not significant differences were detectable between aortic arch and descending thoracic aorta, except for the glutathione transferase activity (0.395 +/- 0.031 vs 0.330 +/- 0.053 U/mg protein, p less than 0.05). Furthermore, both aortic arch and descending thoracic aorta showed significantly higher values of non proteic thiol compounds (46.05 +/- 10.15% and 33 +/- 13.5%, p less than 0.05), selenium-dependent glutathione peroxidase activity (70.35 +/- 26% and 54.3 +/- 9.5%, p less than 0.05), glutathione reductase activity (25.4 +/- 7% and 18.4 +/- 4.5%, p less than 0.05) and thiobarbituric acid reactive substances (65.8 +/- 18% and 47.2 +/- 17%, p less than 0.05) with respect to the abdominal aorta. The selenium-independent glutathione peroxidase activity was not detectable. In conclusion, a biochemical gradient in glutathione-related antioxidant defences and thiobarbituric acid reactive substances proceeding from the proximal to the distal segments seems to exist in the normal rabbit aorta. These results could contribute to explain the non homogeneous distribution of experimental atherosclerosis in the rabbit aorta.     

Hepatic oxidative stress and related defenses during treatment of mice with acetylsalicylic acid and other peroxisome proliferators

The peroxisome proliferators perfluorooctanoic acid (PFOA; 0.02% w/w), perfluorodecanoic acid (PFDA; 0.02%, w/w), nafenopin (0.125%, w/w), clofibrate (0.5%, w/w), and acetylsalicylic acid (ASA; 1%, w/w) were administered to male C57 BL/6 mice in their diet for two weeks. Parameters for Fe³⁺ ADP, NADPH or ascorbic acid-initiated lipid peroxidation in vitro were measured. Approximately a twofold increase in susceptibility to lipid peroxidation was obtained for all the peroxisome proliferators tested. Cotreatment of mice with the peroxisome proliferator ASA (1%, w/w) and a catalase inhibitor, 3-amino-1,2,4-triazole (AT; 0.4%, w/w) for 7 days resulted in little inhibition of peroxisome proliferation, an elevated level of H₂O₂ in vivo, and total inhibition of the increased susceptibility to lipid peroxidation in vitro. No increase in lipid peroxidation in vivo was observed. Certain antioxidant enzymes (DT-diaphorase, superoxide dismutase, glutathione transferase, glutathione peroxidase, and glutathione reductase) and components (ubiquinone and α-tocopherol) were also measured. The results showed that there was some induction of these antioxidant enzymes and components by ASA or aminotriazole, except for glutathione peroxidase and superoxide dismutase, which were inhibited. The possible involvement of oxidative stress in the carcinogenicity of peroxisome proliferators is discussed.     

The modulatory influence of p-methoxycinnamic acid, an active rice bran phenolic acid, against 1,2-dimethylhydrazine-induced lipid peroxidation, antioxidant status and aberrant crypt foci in rat colon carcinogenesis

We investigated the chemopreventive effect of p-methoxycinnamic acid (p-MCA), an active phenolic acid of rice bran, turmeric, and Kaemperfia galanga against 1,2-dimethylhydrazine-induced rat colon carcinogenesis. Male albino Wistar rats were randomly divided into six groups. Group 1 consisted of control rats that received a modified pellet diet and 0.1% carboxymethyl cellulose. The rats in Group 2 received a modified pellet diet supplemented with p-MCA [80 mg/kg body weight (b.wt.) post-orally (p.o.)] everyday. The rats in Groups 3-6 received 1,2-dimethylhydrazine (DMH) (20 mg/kg b.wt.) via subcutaneous injections once a week for the first 4 weeks; additionally, the rats in Groups 4, 5 and 6 received p-MCA at doses of 20, 40 and 80 mg/kg b.wt./day p.o., respectively, everyday for 16 weeks. The rats were sacrificed at the end of the experimental period of 16 weeks. The DMH-treated rats exhibited an increased incidence of aberrant crypt foci (ACF) development; an increased crypt multiplicity; decreased concentrations of tissue lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lipid hydroperoxides (LOOH); decreased levels of tissue enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR); and decreased levels of non-enzymic antioxidants such as reduced glutathione (GSH) and vitamins C, E and A in the colon. Supplementation with p-MCA significantly reversed these changes and significantly inhibited the formation of ACF and its multiplicity. Thus, our findings demonstrate that p-MCA exerts a strong chemopreventive activity against 1,2-dimethylhydrazine-induced colon carcinogenesis by virtue of its ability to prevent the alterations in DMH-induced circulatory and tissue oxidative stress and preneoplastic changes. p-MCA was more effective when administered at a dose of 40 mg/kg b.wt. than at the other two doses tested.     

Antioxidant efficacy of black pepper (Piper nigrum L.) and piperine in rats with high fat diet induced oxidative stress

The present study was aimed to explore the effect of black pepper (Piper nigrum L.) on tissue lipid peroxidation, enzymic and non-enzymic antioxidants in rats fed a high-fat diet. Thirty male Wistar rats (95-115 g) were divided into 5 groups. They were fed standard pellet diet, high-fat diet (20% coconut oil, 2% cholesterol and 0.125% bile salts), high-fat diet plus black pepper (0.25 g or 0.5 g/kg body weight), high-fat diet plus piperine (0.02 g/kg body weight) for a period of 10 weeks. Significantly elevated levels of thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and significantly lowered activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) in the liver, heart, kidney, intestine and aorta were observed in rats fed the high fat diet as compared to the control rats. Simultaneous supplementation with black pepper or piperine lowered TBARS and CD levels and maintained SOD, CAT, GPx, GST, and GSH levels to near those of control rats. The data indicate that supplementation with black pepper or the active principle of black pepper, piperine, can reduce high-fat diet induced oxidative stress to the cells.     

Antioxidant status,lipid peroxidation,mixed function oxidase and UDP-glucuronyl transferase activities in livers from control and DOCA salt-hypertensive male Sprague Dawley rats

The effects of DOCA-salt hypertensive treatment on hepatic glutathione-dependent defense system, antioxidant enzymes, lipid peroxidation, mixed function oxidase and UDP-glucuronyl transferase activities were investigated in male Sprague Dawley rats.Compared with controls, DOCA-salt hypertensive rats had lower body weights (linked to liver hypertrophy). Mixed function oxidase and p-nitrophenol-UGT activities were not affected by the treatment but a significant lower rate of the glucuronoconjugation rate of bilirubin (p < 0.001) was observed in DOCA-salt hypertensive rats. While cytosolic glutathione contents and glutathione reductase activity were not affected, glutathione peroxidase (p < 0.001), glutathione transferase (p < 0.001) and catalase (p < 0.01) activities were decreased and associated with higher malondialdehyde contents (p < 0.001) in treated rats. The imbalance in liver antioxidant status (increasing generation of cellular radical species), associated with increases in lipid peroxidation, suggests that oxidative stress might be directly related to arterial hypertension in DOCA-salt treated male Sprague Dawley rats.     

Low-carbohydrate diet and oxidative stress in diabetic and nondiabetic rats

Hyperglycemia of diabetes has been implicated in increased tissue oxidative stress, with consequent development of secondary complications. Thus, stabilizing glucose levels near normal levels is of utmost importance. Because diet influences glycemic control, this study investigated whether a low-carbohydrate (5.5%) diet confers beneficial effects on the oxidative status of the heart, kidney, and liver in diabetes. Male and female normal and diabetic rats were fed standard chow (63% carbohydrates) or low-carbohydrate diet for 30 days. Elevated glucose, HbA(1c), and alanine and aspartate aminotransferases in diabetic animals were reduced or normalized by the low-carbohydrate diet. While diabetes increased cardiac activities of glutathione peroxidase and catalase, low-carbohydrate diet normalized cardiac glutathione peroxidase activity in diabetic animals, and reduced catalase activity in females. Diabetic rats fed low-carbohydrate diet had altered activities of renal glutathione reductase and superoxide dismutase, but increased renal glutathione peroxidase activity in diabetic animals was not corrected by the test diet. In the liver, diabetes was associated with a decrease in catalase activity and glutathione levels and an increase in glutathione peroxidase and gamma-glutamyltranspeptidase activities. Decreased hepatic glutathione peroxidase activity and lipid peroxidation were noted in diet-treated diabetic rats. Overall, the low-carbohydrate diet helped stabilize hyperglycemia and did not produce overtly negative effects in tissues of normal or diabetic rats.     

Impact of chromium on lipoperoxidative processes and subsequent operation of the glutathione cycle in rat renal system.

Oral administration of K2Cr2O7 to male albino rats at an acute dose of 1500 mg/kg body wt/day for 3 days brought about sharp decrease in the activities of glucose-6-phosphate dehydrogenase and glutathione reductase of kidney epithelial cells. The scavenging system of kidney epithelium is also affected as evident by the highly significant fall in the activities of glutathione peroxidase, superoxide dismutase and catalase which ultimately leads to the increase in lipid peroxidation value in kidney cortical homogenate. However, glutathione-s-transferase activity in cytosol and glutathione and total thiol content in cortical homogenate were not altered. Chronic oral administration of K2Cr2O7 (300 mg/kg body wt/day) for 30 days to rats lead to elevation in the activities of glutathione peroxidase, glutathione reductase, glutathione-s-transferase, superoxide dismutase and catalase with no change in glucose-6-phosphate dehydrogenase activity in epithelial cells. This might lead to the increase in glutathione and total thiol status and decrease in lipid peroxidation value in whole homogenate system.     

Multivitamin and mineral supplementation in 1,2-dimethylhydrazine induced experimental colon carcinogenesis and evaluation of free radical status, antioxidant potential, and incidence of ACF

This study was performed to determine the chemopreventive and antioxidant status of multivitamin and mineral (0.01% in drinking water, ad libitum) supplements in 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis. Experimental colon carcinogenesis was induced in male albino Wistar rats by injecting DMH (20 mg·(kg body mass)(-1)) once weekly for 15 consecutive weeks, and administering a multivitamin supplement in 3 regimes (initiation, post-initiation, and entire experimental period) for 32 weeks. We studied lipid peroxidation products (thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes) in the circulation and in the tissues, antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and non-enzymatic antioxidant-reduced glutathione) of the tissues, aberrant crypt foci (ACF), and histopathological alterations. DMH-induced rats had an increase in lipid peroxidation products and a lower antioxidant status compared with control animals. Multivitamin and mineral supplementation during the initiation, post-initiation, and the entire study period significantly decreased the levels of lipid peroxidation products in circulation and colonic tissues, significantly elevated the activities of the antioxidant enzymes and reduced glutathione to near normalcy in DMH-induced rats. The incidence of ACF was reduced by [corrected] 84.1% in rats supplemented with multivitamin and minerals for the entire study and prevented the colonic tissue from histopathological alterations induced by DMH.     

Effects of new antioxidant compounds PNU-104067F and PNU-74389G on antioxidant defense in normal and diabetic rats

Diabetes mellitus and its complications are associated with elevated oxidative stress, leading to much interest in antioxidant compounds as possible therapeutic agents. Two new classes of antioxidant compounds, the pyrrolopyrimidines and the 21-aminosteroids, are known to inhibit lipid peroxidation and other biomolecular oxidation. We hypothesized that in the presence of excess oxidants or the impaired antioxidant defense seen in diabetes mellitus, administration of antioxidants such as these may reverse the effects of diabetes on antioxidant parameters. This study measured the effects of subchronic (14 day) treatment with a pyrrolopyrimidine (PNU-104067F) or a 21-aminosteroid (PNU-74389G) in normal and diabetic Sprague-Dawley rats. Activity levels of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, concentrations of oxidized and reduced glutathione, and lipid peroxidation were used as measures of antioxidant defense in liver, kidney, heart, and brain tissue. In normal rats, the only effect was a 43% increase in cardiac lipid peroxidation after treatment with PNU-104067F. In diabetic rats, the only reversals of the effects of diabetes were a 30% decrease in hepatic glutathione peroxidase activity after PNU-74389G treatment and a 33% increase in cardiac glutathione disulfide concentration after PNU-104067F treatment. In contrast to these effects, increased cardiac glutathione peroxidase and catalase activities, increased brain glutathione peroxidase activity, increased hepatic lipid peroxidation, decreased hepatic glutathione content, and decreased hepatic catalase activity were seen in diabetic rats, reflecting an exacerbation of the effects of diabetes.     

Effects of piperine on antioxidant pathways in tissues from normal and streptozotocin-induced diabetic rats

Using diabetes mellitus as a model of oxidative damage, this study investigated whether subacute treatment (10 mg/kg/day, intraperitoneally for 14 days) with the compound piperine would protect against diabetes-induced oxidative stress in 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione (GSH and GSSG, respectively) content, and activities of the free-radical detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. Piperine treatment of normal rats enhanced hepatic GSSG concentration by 100% and decreased renal GSH concentration by 35% and renal glutathione reductase activity by 25% when compared to normal controls. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Treatment with piperine reversed the diabetic effects on GSSG concentration in brain, on renal glutathione peroxidase and superoxide dismutase activities, and on cardiac glutathione reductase activity and lipid peroxidation. Piperine treatment did not reverse the effects of diabetes on hepatic GSH concentrations, lipid peroxidation, or glutathione peroxidase or catalase activities; on renal superoxide dismutase activity; or on cardiac glutathione peroxidase or catalase activities. These data indicate that subacute treatment with piperine for 14 days is only partially effective as an antioxidant therapy in diabetes.     

Effects of coenzyme Q10 treatment on antioxidant pathways in normal and streptozotocin-induced diabetic rats

Coenzyme Q10 is an endogenous lipid soluble antioxidant. Because oxidant stress may exacerbate some complications of diabetes mellitus, this study investigated the effects of subacute treatment with exogenous coenzyme Q10 (10 mg/kg/day, i.p. for 14 days) on tissue antioxidant defenses in 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione contents, and activities of catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. All tissues from diabetic animals exhibited increased oxidative stress and disturbances in antioxidant defense when compared with normal controls. Treatment with the lipophilic compound coenzyme Q10 reversed diabetic effects on hepatic glutathione peroxidase activity, on renal superoxide dismutase activity, on cardiac lipid peroxidation, and on oxidized glutathione concentration in brain. However, treatment with coenzyme Q10 also exacerbated the increase in cardiac catalase activity, which was already elevated by diabetes, further decreased hepatic glutathione reductase activity, augmented the increase in hepatic lipid peroxidation, and further increased glutathione peroxidase activity in the heart and brain of diabetic animals. Subacute dosing with coenzyme Q10 ameliorated some of the diabetes-induced changes in oxidative stress. However, exacerbation of several diabetes-related effects was also observed.     

Organoselenium (Sel-Plex diet) decreases amyloid burden and RNA and DNA oxidative damage in APP/PS1 mice

To evaluate potential antioxidant characteristics of organic selenium (Se), double knock-in transgenic mice expressing human mutations in the amyloid precursor protein (APP) and human presenilin-1 (PS1) were provided a Se-deficient diet, a Se-enriched diet (Sel-Plex), or a control diet from 4 to 9 months of age followed by a control diet until 12 months of age. Levels of DNA, RNA, and protein oxidation as well as lipid peroxidation markers were determined in all mice and amyloid β-peptide (Aβ) plaques were quantified. APP/PS1 mice provided Sel-Plex showed significantly (P < 0.05) lower levels of Aβ plaque deposition and significantly decreased levels of DNA and RNA oxidation. Sel-Plex-treated mice showed no significant differences in levels of lipid peroxidation or protein oxidation compared to APP/PS1 mice on a control diet. To determine if diminished oxidative damage was associated with increased antioxidant enzyme activities, brain glutathione peroxidase (GSH-Px), glutathione reductase, and glutathione transferase activities were measured. Sel-Plex-treated mice showed a modest but significant increase in GSH-Px activity compared to mice on a normal diet (P < 0.5). Overall, these data suggest that organic Se can reduce Aβ burden and minimize DNA and RNA oxidation and support a role for it as a potential therapeutic agent in neurologic disorders with increased oxidative stress.