Carnosine prevents testicular oxidative stress and advanced glycation end product formation in D-galactose-induced aged rats.

D-Galactose is shown to mimic natural ageing in rodents by exacerbating oxidative stress and glycation. Steroid production and having a poor antioxidant system make testis vulnerable to galactose-induced ageing. Antioxidation and antiglycating actions of carnosine may be intriguing for prevention of testicular ageing. In this study, male Wistar rats were applied D-galactose (300 mg/kg; subcutaneously 5 days a week) and carnosine (250 mg/kg; intraperitoneally 5 days a week) along with D-galactose for 2 months. D-Galactose treatment increased testicular reactive oxygen species, thiobarbituric acid reactive substances, diene conjugates, protein carbonyls, advanced oxidation products of proteins and advanced glycation end products. Carnosine was capable of repelling oxidative stress and glycation produced by D-galactose. Johnsen's score, which describes histopathological evaluation, was also significantly improved with preserved spermatogenesis by carnosine. It appears that carnosine deters the testicular oxidative stress due to galactose-induced ageing directly by its antioxidative and antiglycating properties.

Effects of carnosine, taurine, and betaine pretreatments on diethylnitrosamine-induced oxidative stress and tissue injury in rat liver.

Several chemicals such as N-diethylnitrosamine (DEN) promote hepatocellular cancer in rodents and induce hepatocyte injury. DEN affects the initiation stage of carcinogenesis together with enhanced cell proliferation accompanied by hepatocellular necrosis. DEN-induced hepatocellular necrosis is reported to be related to enhanced generation of reactive oxygen species. Carnosine (CAR), taurine (TAU), and betaine (BET) are known to have powerful antioxidant properties. We aimed to investigate the effects of CAR, TAU, and BET pretreatments on DEN-induced oxidative stress and liver injury in male rats. Rats were given CAR (2 g L-1 in drinking water), TAU (2.5% in chow), and BET (2.5% in chow) for 6 weeks and DEN (200 mg kg-1 intraperitoneally) was given 2 days before the end of this period. Serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and γ-glutamyl transferase activities were determined and a histopathologic evaluation was performed on the liver tissue. Oxidative stress was detected in the liver by measuring malondialdehyde, diene conjugate, protein carbonyl and nitrotyrosine levels, glutathione and glutathione peroxidase levels, and superoxide dismutase and glutathione transferase activities. Pretreatments with CAR, TAU, and BET decreased liver prooxidant status without remarkable changes in antioxidant parameters in DEN-treated rats. Pretreatments with TAU and BET, but not CAR, were also found to be effective to reduce liver damage in DEN-treated rats. In conclusion, TAU, BET, and possibly CAR may have an ameliorating effect on DEN-induced hepatic injury by reducing oxidative stress in rats.

Duration of priapism is associated with increased corporal oxidative stress and antioxidant enzymes in a rat model.

Ischaemic priapism is characterised by hypoxia, hypercapnia and acidosis with resultant corporal fibrosis. Studies reported decreased erectile recovery after treatment of priapism longer than 36 h. However, a recent study revealed that half of patients with 3 days of priapism achieved recovery after T-shunt, although mechanism remains unclear. We aimed to investigate the effect of priapism duration on oxidative stress and antioxidant enzymes. Twenty-four male rats were divided into four groups. Group 1 served as control. Groups 2, 3 and 4 represented 1, 2 and 4 h, respectively, of priapism induced by vacuum device and rubber band placed at base of erect penis. After 30 min of reperfusion, penectomy and blood withdrawal were performed to investigate levels of malondialdehyde (MDA), protein carbonyl (PC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx). Corporal MDA progressively increased with priapism duration (P = 0.01). Corporal SOD significantly differed between groups 1, 2 and 4. Also, there were significant differences in corporal GPx in groups 1 and 4 (P = 0.004) and groups 2 and 4 (P = 0.01). Corporal CAT was higher in group 4, but multivariable analysis revealed insignificant differences. Plasma MDA of the experimental groups was significantly higher than that of controls. There were no differences among groups in terms of other parameters. Increased antioxidant enzymes according to duration of priapism suggest that immediate treatment to relieve oxidative stress should be initiated in prolonged cases. However, further studies should be conducted to determine resistance mechanisms of the corpora to prolonged ischaemia.

Association between genetic variants in glutathione peroxidase 1 (GPx1) gene, GPx activity and the risk of prostate cancer.

AIM: The aim of this study was to investigate the association between GPx1 Pro198Leu polymorphism with the development and progression of prostate cancer (PCa) and evaluate whether smoking status and advanced age could modify this association. METHODS: A total of 134 PCa patients and 159 healthy control subjects with serum prostate specific antigen (PSA) levels <4 ng/mL and normal digital rectal examination (DRE) findings were enrolled in this prospectively designed study. PCA patients were classified as low (T1 or T2 and N0M0 stages) and high stage disease (T3 or T4 and N0M0 or N1 or M1 stages). GPx1 Pro198Leu polymorphism was determined using polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (95%CI). RESULTS: Compared to the carriers of Pro/Pro genotype, subjects with the variant genotypes (Pro/Leu or Leu/Leu) had significantly higher risk of PCa. The Leu/Leu genotype was correlated with lower GPx activity among both controls and PCa patients. With respect to tumor stage, Leu/Leu genotype was more frequent in patients with high stage disease than those of low stage disease. In stratified analyses, although the variant Leu/Leu genotype was significantly associated with increased risk of PCa in older age, smoking did not alter this association. CONCLUSION: The present data provide evidence that GPx1 Pro198Leu polymorphism may be associated with the development and progression of PCa and older ages may influence the association.between GPx1 Pro198Leu polymorphism and PCa.

The effect of carnosine treatment on prooxidant-antioxidant balance in liver, heart and brain tissues of male aged rats.

Carnosine (beta-alanyl-L: -histidine) is a dipeptide with antioxidant properties. Oxidative damage by free radicals is one of the mechanisms underlying the aging process. This study was done to investigate the effects of carnosine treatment on lipid peroxidation and antioxidant status of liver, heart, brain in male young and aged rats. At the initiation of 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 rats. At the end of this period, malondialdehyde (MDA) and diene conjugate (DC) and protein carbonyl (PC) levels, glutathione (GSH), vitamin E and vitamin C levels and Cu,Zn-superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined in tissues of carnosine-treated young and old rats. Liver and heart, but not brain MDA and DC levels increased significantly in aged rats as compared to young rats. Liver PC levels were also significantly elevated. Significant decreases in GSH and vitamin C levels and SOD activities were detected in liver of aged rats, but vitamin E levels and GSH-Px and GST activities remained unchanged. Non-enzymatic and enzymatic antioxidants did not change in heart and brain of aged rats. Carnosine treatment decreased high MDA, DC and PC levels and caused significant increases in vitamin E level and SOD activity in the liver of aged rats. There were no changes in non-enzymatic and enzymatic antioxidants in the heart and brain of carnosine-treated aged rats. In conclusion, carnosine treatment was found to be useful in the decrease of age-related oxidative stress in the liver.

Increased lipid peroxidation in the liver and kidney and their mitochondrial fractions following buthionine sulfoximine induced glutathione depletion in guinea pigs.

Malondialdehyde (MDA) and diene conjugates (DC) and vitamin C levels and the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were determined in the liver and kidney and their mitochondrial fractions of guinea pigs 48 h after the injection of L-buthionine-(S,R)-sulfoximine (BSO), a glutathione (GSH) depleting agent. In BSO-induced GSH depletion, lipid peroxidation and SOD activities were found to be increased but GSH-Px activities did not change in the liver and kidney and their mitochondrial fractions. In addition, vitamin C levels remained unchanged in the liver and kidney homogenates. These results indicate that GSH depletion may influence oxidative stress in the liver and kidney and their mitochondrial fractions of guinea pigs.

Effect of acute and chronic administration of sodium valproate on lipid peroxidation and antioxidant system in rat liver.

Changes in glutathione and lipid peroxide levels as well as in the activities of superoxide dismutase, glutathione peroxidase, catalase and glutathione-S-transferase have been studied in rats after acute and chronic sodium valproate treatments. Glutathione levels were decreased only after acute sodium valproate treatment. Neither acute nor chronic treatment influenced lipid peroxidation but induced glutathione-S-transferase activity significantly. On the other hand, no alterations in glutathione peroxidase and superoxide dismutase activities were found, except slight induction of catalase activity after acute administration of sodium valproate. These results indicate that sodium valproate treatment did not induce oxidative stress in the liver.