Ugur Cevikbas

Taurine has a protective effect against thioacetamide-induced liver cirrhosis by decreasing oxidative stress

Thioacetamide (TAA) administration (0.3 g/l of tap water for a period of 3 months) to rats resulted in hepatic cirrhosis as assessed by biochemical and histopathological findings. This treatment caused an increase in the levels of malondialdehyde (MDA) and diene conjugates (DCs) and a decrease in the levels of glutathione (GSH), vitamin E, vitamin C and the activities of glutathione peroxidase (GSH-Px) in the liver of rats. Superoxide dismutase (SOD) activities were unchanged. Taurine (2% w/w, added to the chow diet) was administered together with TAA (0.3 g/l of drinking water) for 3 months. Taurine was found to decrease TAA-induced hepatic lipid peroxidation and to increase TAA-depleted vitamin E levels and GSH-Px activities. Histopathological findings also suggested that taurine has an inhibitive effect on TAA-induced hepatic cirrhosis. These results indicate that taurine treatment has a protective effect against TAAinduced liver cirrhosis by decreasing oxidative stress.

Tuberculous peritonitis--reports of 26 cases, detailing diagnostic and therapeutic problems.

Objective To evaluate the clinical presentation, biochemical (ascites and serum) and laparoscopic findings, and to assess the efficacy of triple anti-tuberculous therapy without rifampicin for 6 months in patients with tuberculous peritonitis. Methods Twenty-six tuberculous peritonitis patients (11 male, 15 female) with a mean age of 34.8 ± 3.4 years (range 14–77) were assessed with regard to diagnostic and therapeutic features. Results The most common symptoms and signs were abdominal pain (92.3%) and ascites (96.2%), respectively. Tuberculin skin test (TST) was positive in all patients. An abnormal chest radiography suggestive of previous tuberculosis was present in five patients (19.2%), and two patients (7.7%) had extra-peritoneal (cerebral, pericardial) active tuberculous involvement. In 24 of the 25 patients who underwent laparoscopy with directed biopsy, whitish nodules suggested tuberculous peritonitis; 76% of the biopsy specimens revealed caseating, 20% non-caseating granulomatous inflammation, and 4% non-specific findings. The ascitic fluid of one patient (3.8%) was positive for acid-resistant bacilli, and culture was positive in two patients (7.7%). Twenty-four of the patients were treated for 6 months with isoniazid, streptomycin (total dose 40 g) and pyrazinamide (for the first 2 months and then substituted with ethambutol). Eighteen patients also received methyl prednisolone, initially 20 mg/day, for 1 month. The follow-up period was 19 ± 1.7 months after the end of therapy (range 6–36). Ascites and abdominal pain abated earlier in patients on steroid therapy. All but two of the 24 patients responded to treatment. Conclusion Non-invasive tests such as acid-fast stain and culture of the ascitic fluid are usually insufficient, hence invasive laparoscopy and peritoneal biopsy are necessary for the diagnosis of tuberculous peritonitis if non-invasive tests such as ascites adenosine deaminase activity measurement are not easily available. Triple therapy without rifampicin for 6 months is sufficient to treat tuberculous peritonitis.

Improving Effect of Dietary Taurine Supplementation on the Oxidative Stress and Lipid Levels in the Plasma, Liver and Aorta of Rabbits Fed on a High-Cholesterol Diet

The effect of a high-cholesterol diet with or without taurine on lipids and oxidative stress in the plasma, liver and aorta of rabbits was investigated. The animals were maintained on a basal diet (control), a high-cholesterol diet (HC, 1% w/w), or a high- cholesterol diet supplemented with taurine (HCHT, 2.5% w/w) for two months. Taurine has an ameliorating effect on atherosclerosis together with a decreasing effect on the cholesterol and triglyceride levels in rabbits fed on an HC diet. The HCHT diet caused a significant decrease in the malondialdehyde (MDA) and diene conjugate (DC) levels in the plasma, liver and aorta of rabbits as compared to the HC group. This treatment did not alter the antioxidant system in the liver of rabbits in the HC group. Our findings indicate that taurine ameliorated oxidative stress and cholesterol accumulation in the aorta of rabbits fed on the HC diet and that this effect may be related to its antioxidative potential as well as its reducing effect on serum lipids.

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.

Betaine or taurine administration prevents fibrosis and lipid peroxidation induced by rat liver by ethanol plus carbon tetrachloride intoxication

Summary.The aim of this study was to investigate the effect of betaine or taurine on liver fibrogenesis and lipid peroxidation in rats. Fibrosis was induced by treatment of rats with drinking water containing 5% ethanol and CCl4 (2 × weekly, 0.2 ml/kg, i.p.) for 4 weeks. Ethanol plus CCl4 treatment caused increased lipid peroxidation and disturbed antioxidant system in the liver. Histopathological findings suggested that the development of liver fibrosis was prevented in rats treated with betaine or taurine (1% v/v in drinking water) together with ethanol plus CCl4 for 4 weeks. When hepatic taurine content was depleted with β-alanine (3% v/v in drinking water), portal-central fibrosis induced by ethanol + CCl4 treatment was observed to proceed cirrhotic structure. Betaine or taurine was also found to decrease serum transaminase activities and hepatic lipid peroxidation without any change in hepatic antioxidant system in rats with hepatic fibrosis. In conclusion, the administration of betaine or taurine prevented the development of liver fibrosis probably associated with decreased oxidative stress.

The effect of betaine treatment on triglyceride levels and oxidative stress in the liver of ethanol-treated guinea pigs.

We investigated the effect of betaine supplementation on ethanol induced steatosis and alterations in prooxidant and antioxidant status in the liver of guinea pigs. Animals were fed with normal chow or betaine containing chow (2% w/w) for 30 days. Ethanol (3 g/kg, i.p.) was given for the last 10 days. We found that ethanol treatment caused significant increases in plasma transaminase activities, hepatic triglyceride and lipid peroxide levels. Significant decreases in glutathione (GSH), alpha-tocopherol and total ascorbic acid (AA) levels were also observed, but hepatic superoxide dismutase, glutathione peroxidase and glutathione transferase activities remained unchanged as compared with those in controls. Betaine treatment together with ethanol in guinea pigs is found to decrease hepatic triglyceride, lipid peroxide levels and serum transaminase activities and to increase GSH levels. No changes in alpha-tocopherol and total AA levels and antioxidant enzyme activities were observed with betaine treatment in alcohol treated guinea pigs. In addition, histopathological assessment of guinea pigs showed that betaine reduced the alcoholic fat accumulation in the liver. Based on these data, betaine treatment has a restoring effect on the alterations in triglyceride, lipid peroxide and GSH levels following ethanol ingestion.

Is severe cryptogenic chronic hepatitis similar to autoimmune hepatitis

BACKGROUND/AIMS It has been reported that severe cryptogenic chronic hepatitis may be a subgroup of autoimmune hepatitis. The aims of this study were to investigate the clinical features, liver function tests, human leukocyte antigens and response to immunosuppressive therapy in severe cryptogenic chronic hepatitis, and to compare the findings in such patients with those in patients with autoimmune hepatitis. METHODS History of alcohol and hepatotoxic drug intake, markers of metabolic liver disease, autoantibodies (antinuclear antibody, smooth muscle antibody, antibody to liver/kidney microsome type 1), and viral markers (HBsAg, HBV DNA, anti-HCV, HCV RNA) were negative in all severe cryptogenic chronic hepatitis patients (histological activity index > 9 and alanine aminotransferase level > 2 x normal). Fifteen cryptogenic patients (13 women; mean age, 33 +/- 16 years) and seven autoimmune patients (seven women; mean age, 28 +/- 3.9 years; five type 1; two type 2a) received prednisolone and azathioprine for at least 2 years. RESULTS Cryptogenic chronic hepatitis patients were similar to patients with autoimmune hepatitis with respect to age, sex, clinical presentation, liver function tests and Knodell scores at admission. HLA phenotype frequencies were comparable between cryptogenic and autoimmune groups: BW6 (77% vs. 100%), DR4 (62% vs. 57%), and HLA B8 (15% vs. 43%). The rates of complete and partial remissions achieved during therapy were 87% vs. 57% and 13% vs. 29%, respectively (p > 0.05). CONCLUSIONS The clinical, biochemical and HLA phenotypic features, and the responsiveness to immunosuppressive therapy in severe cryptogenic chronic hepatitis support the idea that it may be an autoimmune liver disease similar to autoimmune hepatitis.

Role of carnosine in preventing thioacetamide-induced liver injury in the rat

Carnosine (beta-alanyl-L-histidine) is a dipeptide with antioxidant properties. Free radicals are involved in the pathogenesis of acute liver injury induced by thioacetamide (TAA). In this study, we investigated the effect of carnosine treatment on TAA-induced oxidative stress and hepatotoxicity. Rats were injected intraperitoneally with TAA (500 mg/kg) and carnosine (250 mg/kg, intraperitoneal) was co-administered with TAA. All animals were killed 24 h after injections. TAA administration resulted in hepatic necrosis, significant increases in plasma transaminase activities as well as hepatic lipid peroxide levels. In addition, hepatic antioxidant system was found to be depressed following TAA administration. When carnosine was co-administered with TAA in rats, plasma transaminase activities were found to approach to normal values in rats. Histological findings also suggested that carnosine has preventive effect on TAA-induced hepatic necrosis. Carnosine treatment caused significant decreases in lipid peroxide levels in TAA-treated rats without any changes in enzymatic and non-enzymatic antioxidants except vitamin E in the liver of rats. Our findings indicate that carnosine, in vivo may have a preventive effect on TAA-induced oxidative stress and hepatotoxicity by acting as an non-enzymatic antioxidant itself.

The effect of carnosine pretreatment on oxidative stress and hepatotoxicity in binge ethanol administered rats.

Carnosine is a dipeptide having strong antioxidant effects. Oxidative stress plays an important role in pathogenesis of alcohol-induced liver injury. In this study, we investigated the effect of carnosine pretreatment on ethanol-induced oxidative stress and hepatotoxicity. Rats were given carnosine (2 g/L in drinking water) for 4 weeks and then ethanol was administered orally to rats at a dose of 5 g/kg every 12 hours for 3 doses totally (binge model). All rats were killed 6 hours after last ethanol injection. Plasma alanine (ALT) and aspartate (AST) transaminase activities and liver triglyceride, malondialdehyde (MDA), diene conjugate (DC), glutathione (GSH), vitamin E and vitamin C levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined. Binge ethanol administration resulted in significant increases in plasma transaminase activities, hepatic triglyceride and lipid peroxide levels. However, GSH, vitamin E, vitamin C levels and GSH-Px and GST activities were found to be decreased following ethanol administration. Macromicrovesicular steatosis was also seen. Carnosine pretreatment appeared to prevent the increase of plasma ALT and AST activities and hepatic MDA and DC levels following ethanol treatment. In addition, hepatic GSH levels increased, but there were no changes in triglyceride, vitamin E, vitamin C levels and SOD, GSH-Px and GST activities, following ethanol treatment in carnosine-pretreated rats. There was also no change in liver histopathological appearance. In conclusion, carnosine prevented the increases in serum transaminase activities and lipid peroxides in liver of ethanol-treated rats, without any change on steatosis in liver.

Melatonin reduces cholesterol accumulation and prooxidant state induced by high cholesterol diet in the plasma, the liver and probably in the aorta of C57BL/6J mice

Abstract:  We examined the hypolipidemic and antioxidative effects of melatonin in plasma, liver and aorta of C57BL/6J mice fed on a high cholesterol (HC) diet. Mice were fed normal mice chow containing 1.5% cholesterol and 0.5% cholic acid for 4 months with or without melatonin (10 mg/L in drinking water) treatment. HC diet was observed to increase cholesterol, triglyceride and diene conjugate (DC) levels in plasma and liver. There was a tendency towards an increase in cholesterol level in the aorta following HC diet. In addition, aortic DC levels were higher than those of control group. No fatty streaks or plaques developed in the aorta of mice following HC diet, but in some sections, derangement of the endothelial layer was detected. Melatonin treatment was found to reduce plasma, liver cholesterol and DC levels as well as liver triglyceride levels in hypercholesterolemic mice. Aortic cholesterol and DC levels were also reduced in hypercholesterolemic mice when given melatonin, although not statistically significant. There were no differences in aortic histopathological findings of mice fed on a HC diet with and without melatonin treatment. In conclusion, our results indicate that melatonin reduces HC diet‐induced cholesterol accumulation and prooxidant state in the plasma, liver and probably in the aorta.