Effects of betaine supplementation on nitric oxide metabolism, atherosclerotic parameters, and fatty liver in guinea pigs fed a high cholesterol plus methionine diet.

OBJECTIVE: The aim of this study was to investigate the effect of high cholesterol (CHOL) and CHOL + methionine (MET) diets on atherogenic and oxidative index parameters and on the factors that influence nitric oxide (NO) bioavailability. Also, attempts were made to determine whether dietary betaine (BET) resulted in any improvement in the changes that occurred after CHOL + MET administration. METHODS: Guinea pigs were fed chow containing 1.5% CHOL with or without 2% MET for 10 wk. A third group received the CHOL + MET + BET diet. Control groups were given standard chow or standard chow + BET. Arginine, NO, nitrotyrosine (NT), and asymmetric dimethylarginine (ADMA) levels; lipid profile; and dimethylarginine dimethylaminohydrolase (DDAH) activity were measured. The liver and aorta were subjected to histopathologic analysis. RESULTS: The CHOL + MET diet caused higher serum CHOL and homocysteine levels, but no further increases were seen in aortic CHOL and diene conjugate (DC) levels and histopathologic lesions as compared with the CHOL group. Hepatic lipids and DC levels were also higher, and histopathologic lesions were more severe. CHOL + MET feeding increased ADMA and NT levels as compared with those of the CHOL-fed group. When BET (1 g/kg body weight/d) was added to the CHOL + MET diet, homocysteine and lipid levels decreased and histopathologic changes were reversed. BET diet decreased serum ADMA and hepatic and aortic DC levels and partly restored DDAH activity. CONCLUSIONS: BET supplementation may be effective in preventing hyperlipidemia, disturbed NO availability, oxidative stress, and the development of fatty liver and atherosclerotic lesions that might result from excess amounts of cholesterol and methionine in the diet.

Carnosine decreased oxidation and glycation products in serum and liver of high-fat diet and low-dose streptozotocin-induced diabetic rats.

High-fat diet (HFD) and low-dose streptozotocin (STZ)-treated rats provide useful animal model for type II diabetes mellitus. Oxidative stress and advanced glycation end products (AGEs) play a role in the development of diabetic complications. Carnosine (CAR) has anti-oxidant and anti-glycating properties. We investigated the effects of CAR on oxidation and glycation products in HFD+STZ rats. Rats were fed with HFD (60% of total calories from fat) for 4 weeks, and then a single dose of STZ (40 mg/kg; i.p.) was applied. Rats with blood glucose levels above 200 mg/dl were fed with HFD until the end of the 12th week. CAR (250 mg/kg body weight; i.p.; five times a week) was administered to the rats for the last four weeks. CAR significantly decreased serum triglyceride (TG) (57.7%), cholesterol (35.6%) levels and hepatic marker enzyme activities of HFD+STZ rats. It significantly reduced serum reactive oxygen species (ROS) (23.7%), AGEs (13.4%) and advanced oxidized protein products (AOPP) (35.9%) and hepatic TG (59%), ROS (26%), malondialdehyde (MDA) (11.5%), protein carbonyl (PC) (19.2%) and AGE (20.2%) levels. Liver steatosis and hepatocyte ballooning were also significantly reduced. However, CAR treatment did not alter serum glucose and blood glycated haemoglobin and hepatic anti-oxidant enzyme activities/mRNA expressions in HFD+STZ rats. Our results indicate that CAR decreased accumulation of oxidation and glycation products, such as MDA, AGE, AOPP and PC in the serum and liver and ameliorated hepatic dysfunction in HFD+STZ rats. This effect may be related to its anti-oxidative, anti-glycating, and anti-lipogenic potential.

The effect of N-acetylcysteine supplementation on serum homocysteine levels and hepatic and renal oxidative stress in homocysteine thiolactone-treated rats.

The effect of N-acetylcysteine (NAC) (1 g/kg body weight/day) on serum homocysteine (Hcy) levels, insulin resistance (IR), and hepatic and renal prooxidant-antioxidant balance was evaluated in rats treated with homocysteine thiolactone (HcyT) (500 mg/kg body weight/day for 6 weeks). Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione, ferric reducing antioxidant power, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined in the liver and kidney. HcyT elevated serum Hcy levels and caused IR, but liver and kidney function tests remained unchanged. HcyT increased ROS and MDA without any change in hepatic antioxidants, but it elevated renal SOD and GSH-Px activities. NAC decreased serum Hcy, hepatic and renal ROS and MDA levels, and renal SOD and GSH-Px activities in rats with high Hcy levels. However, it did not ameliorate IR. Our results indicate that NAC supplementation may be effective in decreasing Hcy levels and Hcy-induced hepatic and renal oxidative stress.

Blueberry treatment attenuated cirrhotic and preneoplastic lesions and oxidative stress in the liver of diethylnitrosamine-treated rats.

Diethylnitrosamine (DEN)-induced liver cancer normally develops in stages that progress from cirrhosis and carcinoma. Increased oxidative stress is suggested to play a role in DEN-induced carcinogenicity. Blueberries (BB) contain high antioxidant capacity. We investigated the effect of BB supplementation on development of DEN-induced cirrhosis and neoplastic lesions in the liver. Rats were injected with DEN (200 mg/kg; i.p.) three times with an interval of 15 days at 4, 6, and 8 weeks and sacrificed 8 weeks after the last DEN injection. They were also fed on 8% BB (w/w) containing chow for 16 weeks. Hepatic damage markers in serum were determined together with hepatic histopathological examinations. Hydroxyproline (HYP), malondialdehyde (MDA), diene conjugate (DC), protein carbonyl (PC), and glutathione (GSH) levels, and CuZn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, and their mRNA expressions were measured. Protein and mRNA expressions of glutathione transferase-pi (GST-pi) were evaluated as a marker of preneoplastic lesions. BB supplementation decreased hepatic damage markers in serum and hepatic MDA, DC, and PC levels, but SOD, CAT, and GSH-Px activities and their mRNA expressions remained unchanged in DEN-treated rats. BB attenuated cirrhotic changes and decreased hepatic HYP levels and GST-pi expressions. Our results indicate that BB is effective in decreasing development of DEN-induced hepatic cirrhosis and preneoplastic lesions by acting as an antioxidant (radical scavenger) itself without affecting activities and mRNA expressions of antioxidant enzymes.

Carnosine and taurine treatments diminished brain oxidative stress and apoptosis in D-galactose aging model.

D-galactose (GAL) has been used as an animal model for brain aging and antiaging studies. GAL stimulates oxidative stress in several tissues including brain. Carnosine (CAR; ß-alanil-L-histidine) and taurine (TAU; 2-aminoethanesulfonic acid) exhibit antioxidant properties. CAR and TAU have anti-aging and neuroprotective effects. We investigated the effect of CAR and TAU supplementations on oxidative stress and brain damage in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) or TAU (2.5% w/w; in rat chow) for 2 months. Brain malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione transferase (GST) and acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brains by immunohistochemistry. GAL treatment increased brain MDA and PC levels and AChE activities. It decreased significantly brain GSH levels, SOD and GSH-Px but not GST activities. GAL treatment caused histopathological changes and increased apoptosis. CAR and TAU significantly reduced brain AChE activities, MDA and PC levels and elevated GSH levels in GAL-treated rats. CAR, but not TAU, significantly increased low activities of SOD and GSH-Px. Both CAR and TAU diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. Our results indicate that CAR and TAU may be effective to prevent the development of oxidative stress, apoptosis and histopathological deterioration in the brain of GAL-treated rats.

Effect of olive leaf extract treatment on doxorubicin-induced cardiac, hepatic and renal toxicity in rats.

Doxorubicin (DOX) is known to increase in oxidative stress in several organs. Olive leaf extract (OLE) has potent antioxidant effects; therefore, we evaluated the ability of OLE to reduce DOX-induced toxicity in the heart, liver, and kidneys of rats. DOX (30mg/kg; i.p.) was administered to rats, which were sacrificed 4 days after DOX. The rats received OLE (6 and 12mL/L in drinking water) for 12 days. Serum cardiac troponin I (cTnI) levels, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities, urea and creatinine levels, as well as prooxidant and antioxidant status in organs were measured. DOX was found to increase serum markers that indicate tissue injury, malondialdehyde (MDA), diene conjugate (DC), and protein carbonyl (PC) levels, and to decrease glutathione (GSH) levels in organs. Histopathologic changes were also evaluated. OLE, especially OLE 1000, led to decreases in serum cTnI and urea levels, ALT and AST activities, and amelioration in histopathologic findings. Decreases in MDA, DC, and PC, and increases in GSH levels were observed in organs of DOX-treated rats due to OLE. We conclude that OLE treatment may be effective in decreasing DOX-induced cardiac, hepatic and renal oxidative stress and injury.

Blueberry treatment decreased D-galactose-induced oxidative stress and brain damage in rats.

D-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of whole fresh blueberry (BB) (Vaccinium corymbosum L.) treatment on oxidative stress in age-related brain damage model. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with 5 % (BB1) and 10 % (BB2) BB containing chow for two months. Malondialdehyde (MDA),protein carbonyl (PC) and glutathione (GSH) levels, and Cu Zn-superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities as well as acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brain by immunohistochemistry. MDA and PC levels and AChE activity increased, but GSH levels, SOD and GSH-Px activities decreased together with histopathological structural damage in the brain of GAL-treated rats. BB treatments, especially BB2 reduced MDA and PC levels and AChE activity and elevated GSH levels and GSH-Px activity. BB1 and BB2 treatments diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. These results indicate that BB partially prevented the shift towards an imbalanced prooxidative status and apoptosis together with histopathological amelioration by acting as an antioxidant (radical scavenger) itself in GAL-treated rats.

Olive leaf extract decreases age-induced oxidative stress in major organs of aged rats.

AIM: Olive leaf (Olea europaea L.) extract (OLE) is a powerful anti-oxidant rich in polyphenols. As oxidative stress plays an important role in aging, we investigated the effect of OLE on oxidative stress in the liver, heart and brain of aged rats. METHODS: Young (age 3 months) and aged (age 20 months) Wistar rats were used. Aged rats received OLE (500 and 1000 mg/kg/day) in drinking water for 2 months. Malondialdehyde (MDA), diene conjugate (DC), protein carbonyl (PC), glutathione (GSH), vitamin E and vitamin C levels, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined. RESULTS: MDA, DC and PC levels increased in tissues of aged rats. GSH levels decreased in the liver, but not in the heart and brain. There was no change of other anti-oxidant parameters in tissues. Hepatic SOD and GSH-Px protein expressions also remained unchanged. OLE treatment caused decreased tissue MDA, DC and PC levels, and increased hepatic GSH levels in aged rats. Other anti-oxidant parameters, hepatic SOD and GSH-Px protein expressions did not alter in aged rats by OLE treatment. CONCLUSION: The present results suggest that OLE seems to be useful for decreasing oxidative stress in examined tissues by acting as an anti-oxidant itself without affecting the anti-oxidant system.

Effects of Ginkgo biloba extract on spinal cord ischemia-reperfusion injury in rats.

BACKGROUND: We aimed to assess the biochemical and histopathologic effects of Ginkgo biloba extract (EGb) in an ischemia-reperfusion (IR) model of spinal cord ischemia induced by cross-clamping of the infrarenal abdominal aorta. METHODS: A total of 24 Sprague-Dawley rats were divided into 3 groups as group 1: control (sham laparotomy), group 2: IR, and group 3: IR+EGb treatment (IR+T) group. All subjects were euthanized 2 days postsurgery and their spinal cords were removed. Tissue malondialdehyde, superoxide dismutase, glutathione (GSH), and glutathione peroxidase levels were measured, and the spinal cord tissue samples were examined histopathologically. RESULTS: No significant difference was detected in ischemia markers between control, IR, and IR+T groups, with the exception of GSH, which was significantly lower in the IR group. GSH levels in group 1 and group 3 were similar. The group 2 displayed significant ischemic damage to the medulla spinalis. This damage was less pronounced in group 3 compared with group 2 only, but in extent and intensity comparable with the controls. CONCLUSIONS: Although we were not able to demonstrate a uniform effect of EGb on biochemical markers of IR injury, the histopathologic data appear to show a protective effect conferred on the spinal cord tissue by EGb.

Blueberry treatment attenuates D-galactose-induced oxidative stress and tissue damage in rat liver.

AIM: d-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of whole fresh blueberry (BB; Vaccinium corymbosum L.) treatment on oxidative stress in age-related liver injury model. METHODS: Rats received GAL (300 mg/kg, s.c.; 5 days per week) alone or together with 5% (BB1) and 10% (BB2) BB-containing chow for 2 months. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and hepatic malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels, and CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and glutathione transferase (GST) activities together with mRNA expressions of SOD1, GPx1, MnSOD (SOD2) and phospholipid hydroperoxide glutathione peroxidase (GPx4) were determined in GAL-treated rats. RESULTS: MDA and PC levels increased, but GSH levels, SOD1 and GPx1 activities decreased together with histopathological structural damage in the liver in GAL-treated rats. There was no change in hepatic mRNA expressions of SOD2 and GPx1, but SOD1 and GPx4 expressions decreased. BB1 and BB2 caused significant decreases in serum ALT and AST activities together with the amelioration in histopathological findings in GAL-treated rats. Both BB1 and BB2 reduced MDA and PC levels, and elevated GSH levels, and SOD1 and GPx1 activities. However, hepatic mRNA expressions of SOD1, SOD2, GPx1 and GPx4 remained unchanged in GAL-treated rats. CONCLUSIONS: These results show that BB restored liver pro-oxidant status together with histopathological amelioration by acting as an anti-oxidant (radical scavenger) itself without affecting mRNA expressions of anti-oxidant enzymes in GAL-treated rats.

Effect of blueberry pretreatment on diethylnitrosamine-induced oxidative stress and liver injury in rats.

Diethylnitrosamine (DEN) treatment increases the generation of reactive oxygen species (ROS), apoptosis, necrosis and proliferation in the liver. Blueberries (BB; Vaccinium corymbosum L.) contain polyphenols and other active components and have high antioxidant capacities. We investigated the effect of BB pretreatment on DEN-induced liver injury and oxidative and nitrosative stress in male rats. Rats were fed with 5% and 10% BB containing diet for six weeks and DEN (200mg/kg; i.p.) was applied two days before the end of this period. Liver function tests were determined in serum and histopathological evaluation was performed in the liver tissue. Apoptosis-related proteins, Bax and B cell lymphoma-2 (Bcl-2) and proliferating cell nuclear antigen (PCNA) expressions were also examined. Oxidative and nitrosative stress were evaluated in the liver by measuring thiobarbituric acid reactive substances, diene conjugate, protein carbonyl and nitrotyrosine levels, and glutathione levels and glutathione peroxidase, superoxide dismutase and glutathione transferase (GST) activities. Pretreatment with high dose of BB reduced apoptotic, necrotic and proliferative changes in the liver induced by DEN. Dietary BB also decreased hepatic lipid peroxidation, protein oxidation and nitrotyrosine levels together with increased GST activity. In conclusion, BB may have an inhibiting effect on acute liver injury by reducing apoptosis, necrosis, proliferation, oxidative and nitrosative stress in DEN-treated rats.

Effect of carnosine treatment on oxidative stress in serum, apoB-containing lipoproteins fraction and erythrocytes of aged rats.

One of the mechanisms underlying the aging process is proposed to be oxidative damage by free radicals. Carnosine (ß-alanyl-L-histidine) is a dipeptide with antioxidant properties. In this study, we investigated the effect of carnosine supplementation on oxidative stress in serum, apoB-containing lipoproteins (LDL + VLDL) and erythrocytes of young and aged rats. At the initiation of the study, young and aged rats were 5 and 22 months old, respectively. Carnosine (250 mg/kg, daily, i.p.) was administered for 1 month to young and aged rats. We found that serum malondialdehyde (MDA) and diene conjugate (DC) levels and endogenous DC and copper-induced MDA levels in the LDL+ VLDL fraction increased in aged rats, but there was no change in plasma antioxidant activity. Endogenous DC and H(2)O(2)-induced MDA levels were also higher, but glutathione (GSH) levels were lower in erythrocytes of aged rats. Administration of carnosine for 1 month to aged rats resulted in decreased levels of MDA and DC in serum, the LDL + VLDL fraction and erythrocytes and increased levels of GSH in erythrocytes. Our findings indicate that in vivo carnosine treatment may be useful for the decrease in aged-induced oxidative stress in serum, the LDL + VLDL fraction and erythrocytes.

Effect of artichoke leaf extract on hepatic and cardiac oxidative stress in rats fed on high cholesterol diet.

Hypercholesterolemia and lipid peroxidation play complementary roles in atherosclerosis. Artichoke (Cynara scolymus L., Asteraceae) leaf extract (ALE), rich in antioxidants, has cholesterol-reducing effect. We investigated the effect of ALE on serum and hepatic lipid levels and pro-oxidant-antioxidant balance in the liver and heart of hypercholesterolemic rats. Rats were fed on 4% (w/w) cholesterol and 1% cholic acid (w/w) supplemented diet for 1 month. ALE (1.5 g/kg/day) was given by gavage during the last 2 weeks. High cholesterol (HC) diet caused significant increases in serum and liver cholesterol and triglyceride levels. It increased malondialdehyde (MDA) and diene conjugate (DC) levels in both tissues. Hepatic vitamin E levels and hepatic and cardiac glutathione peroxidase (GSH-Px) activities decreased, but superoxide dismutase and glutathione transferase activities, glutathione, and vitamin C levels remained unchanged due to HC diet. Serum cholesterol and triglyceride levels and ratio of cholesterol to high-density lipoprotein (HDL)-cholesterol decreased in ALE plus HC-treated rats, but liver cholesterol and triglyceride levels remained unchanged. Significant decreases in hepatic and cardiac MDA and DC levels and increases in hepatic vitamin E and GSH-Px activities were observed in ALE-treated hypercholesterolemic rats. Our results indicate that ALE decreases serum lipids and hypercholesterolemia-induced pro-oxidant state in both tissues.

Effects of high methionine diet on oxidative stress in serum, apo-B containing lipoproteins, heart, and aorta in rabbits.

This study investigated in rabbits whether a high methionine (HM) diet influences oxidative stress parameters in serum, apo-B containing lipoproteins (LDL+VLDL), heart, and aorta. Rabbits received a normal commercial chow supplemented with 2% L-methionine (w/w) for 6 mo (approximately 1 g/kg body wt/day). Serum homocysteine (HCys), malondialdehyde (MDA), diene conjugate (DC), and cholesterol levels were found to be increased, but protein carbonyl (PC) and triglyceride levels remained unchanged in the HM group as compared to controls. Cholesterol, endogenous DC, and copper-induced MDA levels were significantly higher in the LDL+VLDL fraction of plasma lipoproteins in the HM group. MDA and DC levels were found to be increased in homogenates of heart and aorta in the HM group. The HM diet caused significant increases in cardiac glutathione peroxidase activity, but glutathione, vitamin E, and vitamin C levels and superoxide dismutase and glutathione transferase activities remained unchanged. There were no significant differences in the cholesterol levels and histopathological findings in the aortas of the control vs the HM group. This study demonstrates that a HM diet induces oxidative stress in serum, apo-B containing lipoproteins, heart, and aorta in rabbits.

Effect of taurine treatment on pro-oxidant-antioxidant balance in livers and brains of old rats.

The effect of taurine treatment on antioxidant defense in liver and brain tissues of old rats was investigated. Endogenous malondialdehyde (MDA) and diene conjugate (DC), ascorbic acid (AA)- and NADPH-induced lipid peroxide levels as well as non-enzymatic (glutathione--GSH, vitamin E and vitamin C) and enzymatic antioxidants (superoxide dismutase, glutathione peroxidase and glutathione transferase) were determined in livers and brains of young (5 months), old (22 months), and taurine-treated old rats. Taurine (2%, w/v; in drinking water) was administered to old rats for 6 weeks. Taurine levels decreased in the liver and brain of old rats compared to young rats.MDA and DC levels increased, GSH levels decreased, but induced lipid peroxidation remained unchanged in livers of aged rats. Oxidative stress parameters did not change in brains of aged rats. Taurine treatment resulted in significant increases in taurine levels, decreases in MDA and DC levels and increases in GSH levels in livers of old rats. Taurine treatment also increased brain taurine levels. However, no significant changes were detected in lipid peroxidation and antioxidant system in brains of old rats following taurine treatment. Accordingly, in old rats the liver seems more susceptible to age-related lipid peroxidation increases and taurine level changes than the brain. Thus, taurine supplementation seems to be useful for decreasing hepatic oxidative stress in aging.

Effect of pretreatment with artichoke extract on carbon tetrachloride-induced liver injury and oxidative stress.

Artichoke is a plant with antioxidant properties. In this study, we investigated the effect of artichoke extract pretreatment on carbon tetrachloride (CCl4)-induced oxidative stress and hepatotoxicity. Rats were given artichoke leaf extract (1.5g/kg/day) by gavage for 2 weeks and after then CCl4 (1ml/kg; i.p.) was applied. All rats were killed 24h after the CCl4 injection. CCl4 administration resulted in hepatic necrosis and significant increases in plasma transaminase activities as well as hepatic malondialdehyde (MDA) and diene conjugate (DC) levels in the liver of rats. Glutathione (GSH) and vitamin C levels decreased, but vitamin E levels increased in the liver of CCl4-treated rats. Hepatic superoxide dismutase (SOD) activities remained unchanged, but glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities decreased following CCl4 treatment. In rats pretreated with artichoke extract, significant decreases in plasma transaminase activities and amelioration in histopathological changes in the liver were observed following CCl4 treatment as compared to CCl4-treated rats. In addition, hepatic MDA and DC levels decreased, but GSH levels and GSH-Px activities increased without any change in other antioxidant parameters following CCl4 treatment in artichoke-pretreated rats. The present findings indicate that in vivo architoke extract administration may be useful for the prevention of oxidative stress-induced hepatotoxicity.

Lipid peroxidation potential and antioxidants in the heart tissue of beta-alanine- or taurine-treated old rats.

The aim of this study was to investigate the effect of the changes of taurine levels in the hearts of old rats on endogenous malondialdehyde (MDA) and diene conjugate (DC) levels and ascorbic acid (AA)- and NADPH-induced lipid peroxidation as well as non-enzymatic (glutathione, vitamin E and vitamin C) and enzymatic antioxidants (superoxide dismutase, glutathione peroxidase and glutathione transferase). Two groups of old (22 mo) rats were treated with beta-alanine (3%, w/v; in drinking water), a taurine depleting agent, or taurine (2% w/v; in drinking water) for 6 wk. Significant decreases were observed in taurine contents of hearts in old rats as compared to young (5 mo) rats. We found that MDA and DC levels and AA- and NADPH-induced lipid peroxidation increased, but non-enzymatic and enzymatic antioxidants did not alter in heart homogenates of aged rats. beta-Alanine administration resulted in significant decreases in heart taurine levels of old rats. This treatment did not cause further increases in MDA or DC levels or changes in antioxidants. However, AA- and NADPH-induced lipid peroxidation was higher than that of old rats. Taurine treatment caused significant increases in heart taurine levels of old rats. This treatment was found to decrease endogenous MDA and DC levels without affecting the antioxidant system in the heart homogenates of aged rats. AA- and NADPH-induced lipid peroxidation was also reduced in old rats when given taurine, although not statistically significantly. Our results indicate that the changes in heart taurine levels may influence the susceptibility of heart tissue to lipid peroxidation in aged rats and that taurine supplementation has protective effects on age-dependent oxidative stress in heart tissue.

Methionine-supplemented diet augments hepatotoxicity and prooxidant status in chronically ethanol-treated rats.

The purpose of this study was to investigate whether high methionine (HM) diet may influence the development of ethanol-induced hepatotoxicity and prooxidant-antioxidant balance in the liver. Rats received drinking water containing ethanol (20% v/v) and/or methionine supplemented diet (2% w/w) for 75 days. Although prooxidant-antioxidant balance did not change in the liver of rats in HM group, ethanol treatment was observed to increase plasma transaminase activities, and malondialdehyde (MDA) and protein carbonyl (PC) levels, but not glutathione (GSH), vitamin E and vitamin C levels, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities in the liver of rats as compared to controls. However, ethanol plus HM diet caused further increases in plasma transaminase activities and hepatic MDA and PC levels. In addition, SOD, GSH-Px and GST activities were observed to decrease, but GSH, vitamin E and vitamin C levels remained unchanged in the liver as compared to ethanol, HM and control groups. Our results show that HM diet may augment hepatotoxicity and oxidative stress in the liver of chronically ethanol-treated rats.

The effect of chronic diazepam administration on lipid peroxidation and Ca2+ -ATPase activity in rat liver.

Chronic administration of diazepam (DZP) caused an increase in malondialdehyde (MDA) levels and a decrease in glutathione (GSH) content. DZP also markedly lowered Ca2+ATPase activity. Treatment with Se plus vitamin E reduced MDA levels and increased GSH content. Our results suggest that, increased lipid peroxidation together with alteration in Ca2+ -ATPase activity may play a role in DZP induced hepatic injury and Se plus vitamin E treatment may contribute to the attenuation of DZP induced hepatotoxicity.

Methionine supplementation did not augment oxidative stress, atherosclerotic changes and hepatotoxicity induced by high cholesterol diet in C57BL/6J mice.

The purpose of this study was to investigate the effect of a high-methionine plus cholesterol diet (HM+HC) on plasma, erythrocyte, liver and aorta lipid, lipid peroxide levels, and the liver antioxidant system, as well as hepatic and aortic histopathology in CS 7BL/6J mice, and to compare these results to those observed following administration of a high-methionine (HM) or high-cholesterol diet (HC) alone. Mice were fed diets containing 1.5% methionine, 1.5%, cholesterol and 0.5% cholic acid, or a combination of the two diets, for 4 mo. The HM diet did not alter cholesterol or diene conjugate (DC) levels in the plasma or aorta, but this diet caused increases in cholesterol, triglyceride, malondialdehyde (MDA) and DC levels and a decrease in a-tocopherol levels without any change in the levels of glutathione and ascorbic acid or the activities of superoxide dismutase, glutathione peroxidase and glutathione transferase in the liver of mice. However, the HC diet alone was found to further increase cholesterol, triglyceride. MDA and DC levels in the plasma and liver together with changes in hepatic antioxidant system elements, but aortic cholesterol and DC levels remained unchanged as compared to the control group. There were no changes in blood hemoglobin and erythrocyte MDA levels or erythrocyte hemolysis values in both the HM and HC groups. However, the parameters related to lipid and lipid peroxide and antioxidant systems did not change in the plasma or tissues of the HM+HC and HC groups. Only plasma cholesterol was observed to increase in the HM+HC group as compared to the HC group. In addition, histopathological findings in the liver and aorta were similar in the HC and HM+HC groups. In conclusion, our results indicate that the addition of methionine to the HC diet did not augment oxidative stress, hepatotoxicity or atherosclerotic changes induced by the HC diet in mice.