The effect of resveratrol on glycation and oxidation products in plasma and liver of chronic methylglyoxal-treated rats.

BACKGROUND: Methylglyoxal (MG) is a highly reactive dicarbonyl compound. It is produced by processes like glycolysis, glucose autooxidation, lipid peroxidation, and protein glycation. It is a major precursor of advanced glycation end products (AGE). It also exacerbates oxidative stress in the organism. Although there are some in vitro studies investigating the effect of resveratrol (RES) as an antioxidant and antiglycating agent on MG-induced toxicity, in vivo effect of RES is unknown. Therefore, we aimed to investigate the efficiency of RES in chronic MG-treated rats. METHODS: Rats were given incrementally increased doses (100-300 mg/kg) of MG in drinking water for ten weeks. RES (10 mg/kg ip) was administered together with MG. Reactive oxygen species (ROS) formation, thiobarbituric reactive substances (TBARS), protein carbonyl (PC), advanced oxidation protein products (AOPP) and AGE levels as well as ferric reducing antioxidant power (FRAP) values were determined in plasma and liver. RESULTS: Significant increases in plasma TBARS, PC, AOPP and AGE and fructosamine levels were detected in MG-treated rats. However, plasma ROS and FRAP levels remained unchanged. Hepatic ROS, TBARS, PC and AOPP, but not AGE and FRAP levels were also increased in MG-treated rats. RES treatment diminished high levels of plasma PC, AOPP and AGE levels in MG-treated rats. Additionally, significant decreases in hepatic ROS, TBARS, PC and AOPP levels together with histopatological amelioration were detected due to RES treatment in MG-treated rats. CONCLUSIONS: Our results indicate that RES may be considered as a protective agent against glycoxidative stress generated by in vivo MG treatment.

Carnosine Treatment Diminished Oxidative Stress and Glycation Products in Serum and Tissues of D-Galactose-Treated Rats.

BACKGROUND: Chronic administration of D-galactose (GAL) induces changes that resemble natural aging in rodents. Oxidative stress and Advanced Glycation End products (AGE) formation play a role in GAL-induced aging. Carnosine (CAR; ß-alanyl-L-histidine) has antioxidant and anti-glycating actions and may be a potential therapeutic agent in aging due to these properties. The effect of CAR supplementation on AGE levels and oxidative stress parameters was investigated in serum, liver and brain tissues in GAL-treated rats. METHODS: 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) was applied to male rats for two months. AGE, Advanced Oxidized Protein Products (AOPP), Protein Carbonyl (PC) and Malondialdehyde (MDA) levels together with Reactive Oxygen Species (ROS) formation and Ferric Reducing Antioxidant Power (FRAP) values were determined. RESULTS: GAL treatment elevated AGE levels, ROS formation and protein and lipid oxidation products in serum and examined tissues. CAR treatment was observed to decrease significantly glycooxidative stress in serum, liver and brain tissues of GAL-treated rats. CONCLUSION: Our results indicate that CAR may be useful for decreasing oxidative stress and glycation products in GAL-induced aging model in rats.

The effect of carnosine on methylglyoxal-induced oxidative stress in rats.

Methylglyoxal (MG) is generated from glycolytic metabolites, lipid peroxidation, glucose autooxidation and protein glycation. It is a prooxidant inducing oxidative stress and formation of advanced glycation end products (AGE). Effect of carnosine (CAR) as an antioxidant on toxicity due to MG has generated interest. In this study, rats were given incrementally increased doses (100-300 mg/kg) of MG in drinking water for ten weeks. CAR (250 mg/kg i.p.) was administered with MG. Plasma thiobarbituric reactive substances (TBARS), protein carbonyl (PC), advanced oxidation protein products (AOPP) and AGE levels were elevated by MG, and CAR decreased PC, AOPP and AGE levels. MG increased liver reactive oxygen species (ROS), TBARS, PC and AOPP levels, which were decreased by CAR. Thus, in vivo role of CAR on chronic MG administration was observed to suppress the generated hepatic and plasma oxidative stress.

Protective effects of carnosine alone and together with alpha-tocopherol on lipopolysaccharide (LPS) plus ethanol-induced liver injury.

The aim of this study was to investigate the effect of carnosine (CAR) alone and together with vitamin E (Vit E) on alcoholic steatohepatitis (ASH) in rats. ASH was induced by ethanol (3 times; 5 g/kg; 12 h intervals, via gavage), followed by a single dose of lipopolysaccharide (LPS; 10 mg/kg; i.p.). CAR (250 mg/kg; i.p.) and Vit E (200 mg D-α-tocopherol/kg; via gavage) were administered 30 min before and 90 min after the LPS injection. CAR treatment lowered high serum transaminase activities together with hepatic histopathologic improvements in rats with ASH. Reactive oxygen species formation, malondialdehyde levels, myeloperoxidase activities and transforming growth factor ß1 (TGF-ß1) and collagen 1α1 (COL1A1) expressions were observed to decrease. These improvements were more remarkable in CAR plus Vit E-treated rats. Our results indicate that CAR may be effective in suppressing proinflammatory, prooxidant, and profibrotic factors in the liver of rats with ASH.

Effects of carnosine on prooxidant-antioxidant status in heart tissue, plasma and erythrocytes of rats with isoproterenol-induced myocardial infarction.

Rats were injected with isoproterenol (ISO; 110 mg/kg, ip, 2 doses, 24 h interval) to induce acute myocardial infarction (AMI) and were sacrificed 6 and 24 h after the last ISO injection. The heart tissue, plasma and erythrocytes of these rats were evaluated for cardiac markers and oxidative stress parameters. Levels of cardiac troponin T (cTnT) and the activities of creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) in plasma were increased 6 and 24 h after ISO treatment. The levels of malondialdehyde (MDA), diene conjugate (DC), and protein carbonyl (PC) were increased in heart tissue and plasma, while levels of erythrocyte MDA and glutathione (GSH) and plasma ferric reducing antioxidant power (FRAP) were also increased. However, GSH levels and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) decreased in heart tissue of rats with AMI. We also investigated the effects of carnosine (CAR) treatment on these parameters 24 h after the last ISO injection. CAR (250 mg/kg/day; ip) treatments were carried out either 10 days before ISO injection or 2 days concomitant with ISO. Pretreatment with CAR decreased plasma LDH and AST activities and ameliorated cardiac histopathological changes in ISO-treated rats. Cardiac MDA, DC and PC levels decreased, but GSH levels and SOD and GSH-Px activities increased. However, the increases in plasma MDA and PC levels as well as erythrocyte H(2)O(2)-induced MDA and GSH levels did not change due to CAR pretreatment. In conclusion, our findings indicate that CAR pretreatment may have protective effects on ISO-induced cardiac toxicity by decreasing oxidative stress.

Carnosine and taurine treatments decreased oxidative stress and tissue damage induced by D-galactose in rat liver.

D-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of carnosine (CAR) or taurine (TAU), having antioxidant effects, on hepatic injury and oxidative stress in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days/week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days/week) or TAU (2.5 % w/w; in rat 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 superoxide dismutase (SOD), glutathione peroxidase (GSH-0050x), and glutathione transferase (GST) activities were determined. Hepatic expressions of B cell lymphoma-2 (Bcl-2), Bax and Ki-67 were evaluated. Serum ALT, AST, hepatic MDA, and PC levels were observed to increase in GAL-treated rats. Hepatic Bax expression, but not Bcl-2, increased, Ki-67 expression decreased. GAL treatment caused decreases in GSH levels, SOD and GSH-Px activities in the liver. Hepatic mRNA expressions of SOD, but not GSH-Px, also diminished. CAR or TAU treatments caused significant decreases in serum ALT and AST activities. These treatments decreased apoptosis and increased proliferation and ameliorated histopathological findings in the livers of GAL-treated rats. Both CAR and TAU reduced MDA and PC levels and elevated GSH levels, SOD and GSH-Px (non significant in TAU + GAL group) activities. These treatments did not alter hepatic mRNA expressions of SOD and GSH-Px enzymes. Our results indicate that CAR and TAU restored liver prooxidant status together with histopathological amelioration in GAL-induced liver damage.

The protection by heme oxygenase-1 induction against thioacetamide-induced liver toxicity is associated with changes in arginine and asymmetric dimethylarginine.

This study was designed to investigate the role of HO-1 induction in prevention of thioacetamide (TAA)-induced oxidative stress, inflammation and liver damage. The changes in hepatic dimethylarginine dimethylaminohydrolase (DDAH) activity as well as plasma arginine and asymmetric dimethylarginine (ADMA) levels were also measured to evaluate nitric oxide (NO) bioavailability. Rats were divided into four groups as control, hemin, TAA and hemin + TAA groups. Hemin (50 mg kg(-1) , i.p.) was injected to rats 18 h before TAA treatment to induce HO-1 enzyme expression. Rats were given TAA (300 mg kg(-1) , i.p.) and killed 24 h after treatment. Although TAA treatment produced severe hepatic injury, upregulation of HO-1 ameliorated TAA-induced liver damage up to some extent as evidence by decreased serum alanine transaminase, aspartate transaminase and arginase activities and histopathological findings. Induction of HO-1 stimulated antioxidant system and decreased lipid peroxidation in TAA-treated rats. Myeloperoxidase activity and inducible NO synthase protein expression were decreased, whereas DDAH activity was increased by hemin injection in TAA-treated rats. Induction of HO-1 was associated with increased arginine levels and decreased ADMA levels, being the main determinants of NO production, in plasma of TAA-treated rats. In conclusion, our results indicate that HO-1 induction alleviated increased oxidative stress and inflammatory reactions together with deterioration in NO production in TAA-induced liver damage in rats.

Effect of carnosine on prooxidant-antioxidant balance in several tissues of rats exposed to chronic cold plus immobilization stress.

In this study, we investigated the effect of L-carnosine (CAR) on prooxidant-antioxidant balance in several tissues of rats exposed to chronic stress. Both cold and immobilization stresses were applied to rats at the same time. In the stress group, rats were placed in restraint cages and kept in a cold room (+4°C) for 1 h for 21 days (5 days a week). Rats were injected with CAR (250 mg/kg, i.p.) at 30 min before stress application. Malondialdehyde, diene conjugate, protein carbonyl and nitrotyrosine levels, nonenzymatic (glutathione, vitamin E, and vitamin C), and enzymatic (catalase, superoxide dismutase and glutathione peroxidase) antioxidants were determined in the liver, heart, and brain tissues. Chronic cold plus immobilization stress was observed to affect especially the prooxidant-antioxidant status in the brain tissue of rats. This is the first report showing the beneficial effects of CAR on oxidative stress in the brain in rats exposed to stress.

Beneficial effects of taurine and carnosine in experimental ischemia/reperfusion injury in testis.

PURPOSE: Testicular torsion can be thought of as an ischemia/reperfusion (I/R) injury to the testis. This study aimed to investigate the effects of taurine (TAU) and carnosine (CAR), which are strong antioxidants, on experimental testicular I/R injury model. METHODS: Male Wistar albino rats were divided into four groups with eight animals in each. A sham operation was performed in group 1. To create testicular I/R, the left testis was torsioned 720° for 2 h followed by 2 h of detorsion. Groups 2 (I/R), 3 (I/R + TAU) and 4 (I/R + CAR) received intraperitoneal saline, TAU (250 mg/kg) and CAR (250 mg/kg), respectively, 1 h before detorsion. Thiobarbituric acid reactive substances (TBARS), diene conjugate (DC), protein carbonyls (PC), nonprotein sulfhydryl (NPSH), and vitamin C levels were measured in testis tissues as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Histopathological evaluation was also performed. RESULTS: TBARS, DC, and PC levels were significantly increased in I/R group. TAU and CAR did not alter TBARS levels, but decreased the elevated DC and PC levels. There were no changes in testicular NPSH levels, SOD, and GPx activities in all groups; however, vitamin C significantly decreased in I/R group. CAR treatment was found to increase vitamin C levels as compared to I/R group. Histopathologically, both I/R + TAU and I/R + CAR groups showed significant increase in testicular spermatogenesis in comparison to I/R group. CONCLUSION: Our results indicate that TAU and CAR reduces oxidative stress and may have a protective role in testicular I/R injury.

Effect of binge ethanol treatment on prooxidant-antioxidant balance in rat heart tissue.

Binge drinking of alcohol is known to cause cardiac dysfunction in some drinkers. This study was designed to examine the effect of ethanol on rat heart tissue with an experimental model mimicking human binge drinking. Female Sprague-Dawley rats were given ethanol diluted with normal saline (40%, v:v) by gavage at the dose of 5.0g/kg every 12h for 3 doses as total. Serum activities of lactate dehydrogenase (LDH), creatine phosphokinase (CK) and aspartate transaminase (AST) were determined. Endogenous lipid peroxidation was assessed by measuring the levels of malondialdehyde (MDA) in heart homogenates. In vitro susceptibility of tissues to oxidative stress was assessed by using two different media. Tissue glutathione (GSH) and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined. All serum enzymatic activities were found markedly elevated in ethanol group. Binge ethanol administration significantly enhanced endogenous lipid peroxidation and caused an enhanced in vitro susceptibility to lipid peroxidation. Levels of reduced GSH and GSH-Px and GST activities were found unchanged as compared to controls. SOD activity was found significantly increased. As a conclusion, binge ethanol consumption which was applied to rats to investigate acute tissue injury, appeared to confirm the generation of oxidative stress in rat hearts.