Low Serum Glutathione Peroxidase Activity Is Associated with Increased Cardiovascular Mortality in Individuals with Low HDLc’s

Background Since oxidized LDL is thought to initiate atherosclerosis and the serum glutathione peroxidase (GPx3) reduces oxidized lipids, we investigated whether high GPx3 activity reduces cardiovascular disease (CVD) mortality. Methods We determined GPx3 in stored samples from the Minnesota Heart Survey of 130 participants who after 5 to 12 years of follow-up had died of CVD and 240 controls. Participants were 26 to 85 years old and predominantly white. In a nested case-control, study we performed logistic regressions to calculate odds ratios (OR) adjusted for age, sex, baseline year, body mass index, smoking, alcohol intake, physical activity, total and HDL cholesterols, systolic blood pressure, serum glucose and gamma glutamyltransferase (GTT) activity. The referent was the quartile with the highest GPx3 activity (quartile 4). Results OR’s for CVD mortality for increasing quartiles of GPx3 were 2.37, 2.14, 1.83 and 1.00 (P for trend 0.02). This inverse correlation was confined to those with HDLc’s below the median (P for interaction, 0.006). The OR’s for increasing quartiles of GPx3 in this group were 6.08, 5.00, 3.64 and 1.00 (P for trend, 0.002). Conclusions Individuals with both low HDLc and GPx3 activity are at markedly increased risk for death from CVD

Short term effects of a low-carbohydrate diet in overweight and obese subjects with low HDL-C levels

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to evaluate short-term effects of a low-carbohydrate diet in overweight and obese subjects with low HDL-C levels.</p> <p>Methods</p> <p>Overweight (BMI between 25-30 kg/m²) or obese (BMI over 30 kg/m²) subjects with low HDL-C levels (men with HDL-C <1.03, women <1.29 mmol/l) were invited to the study. A 1400 kcal 75-gram carbohydrate (CHO) diet was given to women and an 1800 kcal 100-gram CHO diet was given to men for four weeks. The distribution of daily energy of the prescribed diet was 21-22% from CHO, 26-29% from protein and 49-53% from fat. Subjects completed a three-day dietary intake record before each visit. Anthropometric indices, body fat ratio, blood lipids, glucose and insulin were measured. Baseline and week-four results were compared with a Wilcoxon signed ranks test.</p> <p>Results</p> <p>Twenty-five women and 18 men participated. Basal median LDL-C level of men was 3.11 and basal median LDL-C level of women was 3.00 mmol/l. After four weeks of a low-carbohydrate diet, the median energy intake decreased from 1901 to 1307 kcal/day, daily energy from carbohydrate from 55% to 33%, body weight from 87.7 to 83.0 kg and HDL-C increased from 0.83 to 0.96 mmol/l in men (p < 0.002, for all). After four weeks of a low-carbohydrate diet, the median energy intake tended to decrease (from 1463 to 1243 kcal, p = 0.052), daily energy from carbohydrate decreased from 53% to 30% (p < 0.001) and body weight decreased from 73.2 to 70.8 kg (p < 0.001) in women, but HDL-C did not significantly change (from 1.03 to 1.01 mmol/l, p = 0.165). There were significant decreases in body mass index, waist circumference, body fat ratio, systolic blood pressure, total cholesterol, triglyceride and insulin levels in all subjects.</p> <p>Conclusions</p> <p>HDL-C levels increased significantly with energy restriction, carbohydrate restriction and weight loss in men. HDL-C levels didn't change in women in whom there was no significant energy restriction but a significant carbohydrate restriction and a relatively small but significant weight loss. Our results suggest that both energy and carbohydrate restriction should be considered in overweight and obese subjects with low HDL-C levels, especially when LDL-C levels are not elevated.</p

Protective Role of Taurine against Arsenic-Induced Mitochondria-Dependent Hepatic Apoptosis via the Inhibition of PKCδ-JNK Pathway

BACKGROUND: Oxidative stress-mediated hepatotoxic effect of arsenic (As) is mainly due to the depletion of glutathione (GSH) in liver. Taurine, on the other hand, enhances intracellular production of GSH. Little is known about the mechanism of the beneficial role of taurine in As-induced hepatic pathophysiology. Therefore, in the present study we investigated its beneficial role in As-induced hepatic cell death via mitochondria-mediated pathway. METHODOLOGY/PRINCIPAL FINDINGS: Rats were exposed to NaAsO(2) (2 mg/kg body weight for 6 months) and the hepatic tissue was used for oxidative stress measurements. In addition, the pathophysiologic effect of NaAsO(2) (10 microM) on hepatocytes was evaluated by determining cell viability, mitochondrial membrane potential and ROS generation. As caused mitochondrial injury by increased oxidative stress and reciprocal regulation of Bcl-2, Bcl-xL/Bad, Bax, Bim in association with increased level of Apaf-1, activation of caspase 9/3, cleavage of PARP protein and ultimately led to apoptotic cell death. In addition, As markedly increased JNK and p38 phosphorylation with minimal disturbance of ERK. Pre-exposure of hepatocytes to a JNK inhibitor SP600125 prevented As-induced caspase-3 activation, ROS production and loss in cell viability. Pre-exposure of hepatocytes to a p38 inhibitor SB2035, on the other hand, had practically no effect on these events. Besides, As activated PKCdelta and pre-treatment of hepatocytes with its inhibitor, rottlerin, suppressed the activation of JNK indicating that PKCdelta is involved in As-induced JNK activation and mitochondrial dependent apoptosis. Oral administration of taurine (50 mg/kg body weight for 2 weeks) both pre and post to NaAsO(2) exposure or incubation of the hepatocytes with taurine (25 mM) were found to be effective in counteracting As-induced oxidative stress and apoptosis. CONCLUSIONS/SIGNIFICANCE: Results indicate that taurine treatment improved As-induced hepatic damages by inhibiting PKCdelta-JNK signalling pathways. Therefore taurine supplementation could provide a new approach for the reduction of hepatic complication due to arsenic poisoning

Effect of vitamin C on glutathione and lipid peroxide levels in rats exposed to water-immersion restraint stress

We have investigated the effect of vitamin C (vit C) on malondialdehyde (MDA) and glutathione (GSH) levels in several tissues of rats treated with water-immersion restraint (WIR) stress. Hepatic and intestinal MDA levels increased significantly but GSH content remained unchanged after WIR stress. MDA levels declined following vit C supplementation. On the other hand, MDA and GSH levels were unchanged although ulcerogenic injury was seen in the stomach. Microscopically, this injury was reduced in the rats who received vit C. These results indicate that vit C may have a protective effect in stress-induced lipid peroxidation and gastric ulceration. Med Sci Res 26:595-597 (C) 1998 Lippincott Wiliiams & Wilkins

The protective effect of taurine against thioacetamide hepatotoxicity of rats

Thioacetamide (TAA) administration (three consecutive intraperitoneal injections of 400 mg/kg at 24-h interval) to rats resulted in hepatic injury as assessed by the measurement of serum transaminase activities and histopathological findings. This treatment caused an increase in the levels of malondialdehyde (MDA), diene conjugates (DCs) and glutathione (GSH) and the activity of superoxide dismutase (SOD), and a decrease in the levels of vitamins E and C and the activity of glutathione peroxidase (GSH-Px) in the liver of rats. Taurine administration (400 mg/kg, i.p., every 12 h and started 24 h prior to the first TAA injection) was found to decrease serum transaminase activities and hepatic lipid peroxidation without any significant change in hepatic antioxidant system. Histopathological findings also suggested that taurine has ameliorated effect on TAA-induced hepatic necrosis. These results indicate that taurine treatment, together with TAA administration, diminished the severity of the liver injury by decreasing oxidative stress due to its possible scavenger effect

Resistance of erythrocytes to lipid peroxidation in cirrhotic rats

Background. The aim of the present study was to investigate erythrocyte prooxidant-antioxidant balance in relation to liver and plasma lipid peroxidation in thioacetamide (TAA)-induced liver cirrhosis in rats