Güldal Mehmetçik

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.

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.

Increased lipid peroxidation in serum and low-density lipoproteins associated with aging in humans.

This study was carried out in 140 healthy subjects who were divided into three subgroups of age: young (21-40 years), mature (41-60 years), and elderly (61-85 years) to investigate lipid peroxides and the antioxidant system in serum and low-density lipoproteins (LDL). Serum levels of cholesterol and LDL-cholesterol increased with age. The elderly group was found to have higher polyunsaturated fatty acid (PUFA) levels, thiobarbituric acid reactive substances (TBARS), diene conjugates, and lower cholesterol-adjusted vitamin E levels and antioxidant activity (AOA) as compared to the young group. No age-related difference was detected in serum vitamin C levels. Age correlated positively with serum cholesterol, LDL-cholesterol, PUFA, TBARS, diene conjugates, and negatively with cholesterol-adjusted vitamin E levels and AOA. In addition, endogenous LDL diene conjugate levels and the susceptibility of LDL to copper-induced lipid peroxidation increased in elderly subjects as compared with young subjects. In addition, positive correlations were detected between age and LDL endogenous diene conjugate levels and TBARS formation after copper incubation. However, the susceptibility of whole serum to copper-induced lipid peroxidation did not change in young and elderly subjects. Our results show that endogenous lipid peroxide levels in serum and LDL, and the susceptibility of LDL to copper-induced oxidation, increased with aging in humans.

Artichoke leaf extract reduces oxidative stress and lipoprotein dyshomeostasis in rats fed on high cholesterol diet.

Hypercholesterolemia and lipid peroxidation play complementary role in atherosclerosis. Artichoke leaf extract (ALE) is rich in natural antioxidants and has a cholesterol‐reducing effect. However, there is no study investigating the effect of ALE on lipid levels and lipid peroxidation in experimental hypercholesterolemic conditions. Rats were fed on 4% (w/w) cholesterol and 1% (w/w) cholic acid supplemented diet for 1 month. ALE (1.5 g/kg/day) was given by gavage during the last 2 weeks. Serum lipid composition, malondialdehyde (MDA) and diene conjugate (DC) levels and plasma antioxidant activity (AOA) were measured. In addition, endogenous DC and copper‐induced MDA levels were determined in apo B‐containing lipoproteins (LDL+VLDL fraction). Serum cholesterol and triglyceride levels and the ratio of cholesterol to HDL‐cholesterol decreased due to ALE treatment in rats fed on HC diet. Significant decreases in serum MDA and DC levels and increases in plasma AOA were detected in serum in ALE‐treated hypercholesterolemic rats. Endogenous DC and copper‐induced MDA levels were also lower in LDL+VLDL fraction due to ALE‐treatment in hypercholesterolemic rats. Our results indicate that ALE may be useful for the prevention of hypercholesterolemia‐induced pro‐oxidant state in LDL+VLDL fraction and the reduction of increased serum cholesterol and triglyceride levels. Copyright

Association of leptin receptor gene Q223R polymorphism on lipid profiles in comparison study between obese and non-obese subjects.

OBJECTIVES Leptin is a hormone secreted from adipocytes. It regulates metabolism and energy homeostasis through the leptin receptor (LEPR) which is localized centrally in hypothalamus as well as in peripheral tissues. The aim of this study was to investigate the association of leptin receptor gene Q223R polymorphism on obesity in association with body mass index (BMI), lipid parameters, plasma leptin levels and homeostasis model assessment of insulin resistance (HOMA-IR). DESIGN AND METHODS The study included 110 obese and 90 non-obese subjects. The LEPR Q223R polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma leptin levels, serum lipid and antropometric parameters were measured. RESULTS No association was found between LEPR gene Q223R polymorphism and BMI in both study and control groups. Strikingly study group with non-obese subjects and with the RR genotype (homozygous mutant) had significantly higher serum total cholesterol (p<0.001) and low density lipoprotein cholesterol (LDL-cholesterol) levels (p<0.05) than QR (heterozygous) and QQ (wild type) genotypes. In obese group, subjects with the RR genotypes had significantly higher triglycerides (p<0.05) levels, waist (p<0.05) and hip circumferences (p<0.001) than the QQ and QR genotypes. CONCLUSIONS Our results suggest that the LEPR gene Q223R polymorphism has an association with waist and hip circumferences in obese group but no direct association with obesity although there is a significant influence on lipid profile both in obese and non-obese subjects.

Age-related changes in plasma lipid peroxidation and antioxidant system in humans and rats.

This study was carried out on young (20-35 years) and old (60-85 years) men and rats (6 vs 22 months) to investigate the effect of aging on plasma lipid peroxidation and the antioxidant system. Plasma polyunsaturated fatty acid (PUFA), total fatty acid (TFA) and malondialdehyde (MDA) levels increased in aged humans and rats compared with young groups. However, plasma MDA/TFA ratios did not increase in aged humans and rats. Plasma vitamin E/TFA, and total thiol content were found to decrease both in aged humans and rats. Plasma antioxidant activity (AOA) decreased only in aged rats. In addition, the susceptibility of VLDL+LDL, apolipoprotein B containing lipoproteins to copper-induced peroxidation increased with aging. It is concluded that aging is associated with some variations in plasma oxidant-antioxidant balance.