Association between alcohol-induced oxidative stress and membrane properties in synaptosomes: A protective role of vitamin E.

Chronic and excessive alcohol consumption leads to various neurological diseases. Synaptosomes are ideal organelles to study the functional properties of the brain in alcoholism. This study focuses on the association between oxidative stress and synaptosomal membrane properties in alcohol treated rats. Sixty day old male albino rats were treated with 20% alcohol at 5g/kg body weight/ day for sixty days. Alcohol administration significantly increased the levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyls with decreased catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD) activities and reduced glutathione (GSH) content in synaptosomes. Further, alcohol administration decreased (cholesterol/phospholipids) C/P ratio in synaptosomal membranes, which was further confirmed using 1,6 diphenyl 1,3 hexatriene (DPH) as fluorescent probe. Moreover, alcohol treatment also increased membrane bound Na+/K+-ATPase, Ca2+-ATPase and Mg2+-ATPase enzyme activities. Correlation (r) analysis revealed that anisotropic (γ) values were strongly associated with lipid peroxidation (r=0.678) and Na+/K+-ATPase activity (r=0.793). The results of the present study clearly indicate that lipid peroxidation was positively correlated (r=0.621) with Na+/K+-ATPase activity and C/P ratio was negatively associated (r=-0.549) in alcohol treated animals. Similar results were found on alcohol treatment (50 and 100mM) of brain synaptosomes in vitro. But with the co-treatment of vitamin E reversed these changes. In conclusion, synaptosomal membranes properties are impaired due to increased oxidative stress, changes in lipid composition, altered fluidity and membrane bound enzyme activities. And treatment with vitamin E renders protection against ethanol-induced membrane alterations.

Gender differences in alcohol-induced oxidative stress and altered membrane properties in erythrocytes of rats.

Alcohol-induced oxidative stress leads to imbalance between reactive oxygen species (ROS) and the antioxidant defense system, resulting in oxidative damage to membrane components such as lipids and proteins, ultimately altering membrane properties. In this study, we assessed oxidative stress status and alterations in erythrocyte membrane properties in alcohol-administered rats with respect to gender difference. Alcohol (20% v/v) administered rats of both genders showed significant changes in plasma lipid profile with elevated nitrite/nitrate levels. Furthermore, alcohol-administration significantly decreased erythrocyte antioxidant enzymes and enhanced erythrocyte membrane lipid peroxidation, cholesterol/phospholipid (C/P) ratio and Na+/K(+)-ATPase activity in both males and females. Besides, anisotropic studies revealed that alcohol-administration significantly decreased erythrocyte membrane fluidity. In conclusion, alcohol-administration significantly increased oxidative stress by decreasing antioxidant status, and subsequent generation of ROS altered membrane properties by altering fluidity and Na+/K(+)-ATPase activity. Female rats were more vulnerable to alcohol-induced biochemical and biophysical changes in plasma and erythrocyte including oxidative stress than male rats.

Amelioration of alcohol-induced oxidative stress by Emblica officinalis (amla) in rats.

The present study was aimed at investigating the ameliorative effect of Emblica (Phyllanthus Emblica L) fruit extract (EFE) against alcohol-induced oxidative changes in plasma biochemical profile in rats. Alcohol administration (5 g/kg body wt/day) for 60 days resulted in significantly (P<0.05) higher levels of plasma nitrite/nitrate (NOx), total bilirubin, creatinine, and abnormalities in lipid and lipoproteins. Moreover, alcohol receiving rats showed significantly (P<0.05) lowered plasma total protein, albumin/globulin (A/G) ratio and uric acid, with no significant change in glucose level. The EFE administration (250 mg/kg body wt/day) to alcohol-administered rats significantly modulated plasma lipids and lipoprotein patterns and also decreased nitrite/nitrate, total bilirubin and creatinine levels. EFE administration to alcohol receiving rats showed a significant (P<0.05) increase in plasma total protein, A/G ratio and uric acid levels. Total cholesterol (r = 0.466), triglycerides (r = 0.574), VLDL-C (r = 0.578), LDL-C (r = 0.225) and total bilirubin (r = 0.419) showed a stronger positive correlation with that of NOx in alcohol-treated rats. The concentration of nitric oxide (NOx) was negatively correlated with HDL-C (r = -0.285) and uric acid (r = 0.392) in alcohol-treated rats. The amelioration of alcohol-induced oxidative stress might be due to the combined effect of phytophenols, such as tannins and flavonoid compounds and vitamin C.

Chronic exposure to pyrethroid-based allethrin and prallethrin mosquito repellents alters plasma biochemical profile.

Continuous exposure of humans to pyrethroid-based mosquito repellents for longer durations may lead to adverse health effects. No information is available on long-term use of these mosquito repellents pertaining to the biochemical changes in human subjects. Therefore, the present study is an attempt to evaluate the status of health in human volunteers exposed to two commercially available mosquito repellent pyrethroids, allethrin and prallethrin, in terms of changes in plasma biochemical profile. Results of this study showed less but significant increase in the levels of plasma glucose, phospholipids, nitrite and nitrate, lipidperoxides with a decrease in plasma cholesterol. No significant changes were observed in the contents of total protein, albumin, globulin, HDL-C and LDL-C. However, SGPT activity increased significantly in persons exposed to only allethrin. Though the present investigation involving a limited number of human subjects indicates the onset of both protective changes as well as derangement in metabolism, a detailed and rigorous study is greatly warranted to arrive at a definite conclusion about the effects of pyrethroid mosquito repellents.

Role of nitric oxide in alcohol-induced changes in lipid profile of moderate and heavy alcoholics.

Biochemical changes in plasma and red cell membrane in moderate and heavy alcoholics were investigated to compare them with teetotalers in the present study. Significant changes in lipid, lipoprotein profile, and lipid peroxidation were evident from the study suggesting the cardioprotective effect in moderate alcoholics, and adverse changes leading to cardiovascular risk in heavy alcoholics. Both nitrite and nitrate levels in plasma of moderate alcoholics increased significantly when compared with teetotalers and the increase is more pronounced in heavy alcoholics. The results of the present study showed no significant difference in osmotic hemolysis in red cells from moderate and heavy alcoholics incubated with NaCl at concentrations ranging from 0.1% to 0.9%. Further, the study showed a possible relationship of nitric oxide (NO) with changes in plasma lipid profile. To sum up, these changes in both moderate and heavy alcoholics clearly indicated the involvement of NO in rendering tolerance to alcohol-induced effects and also in modulation of alcohol effects.

Gluconeogenic substrates and hepatic gluconeogenic enzymes in streptozotocin-diabetic rats: effect of mulberry (Morus indica L.) leaves.

Mulberry (Morus indica L.) leaves, the sole food of the silk worm, were evaluated for antidiabetic effects in streptozotocin (STZ)-diabetic rats. Treatment with dried mulberry leaf powder at 25% of the diet for a period of 8 weeks was found to be remarkably beneficial to STZ-diabetic rats as evidenced by controlled hyperglycemia and glycosuria. In addition, mulberry leaves countered (reversed) the alterations in gluconeogenic substrates in STZ-diabetic rats as indicated by significant reduction in serum pyruvic and lactic acid levels, a significant increase in proteins and a significant decrease in free amino acid, urea, and creatinine levels in blood, and a decreased urinary excretion of urea and creatinine. Anomalies in the activities of hepatic gluconeogenic enzymes associated with impaired glucose homeostasis in STZ-diabetic rats were ameliorated by feeding the mulberry leaf-supplemented diet, indicating that control over hyperglycemia and associated complications in the diabetic state by mulberry leaves is by way of regulation of gluconeogenesis. With respect to all the parameters, mulberry leaves were more effective than the oral hypoglycemic drug glibenclamide.

Prallethrin induced biochemical changes in erythrocyte membrane and red cell osmotic haemolysis in human volunteers.

Changes in biochemical composition in erythrocyte membrane, erythrocytic osmotic haemolysis, and nitrite and nitrate levels in plasma were analyzed in 12 human volunteers who were exposed regularly to prallethrin, a type I pyrethroid mosquito repellent. The results revealed a decrease in cholesterol (C) and phospholipid (P) moieties in erythrocyte membrane with no consequent change in C:P ratio. Further, a significant decrease in the content of phosphatidyl serine suggested that PS is a sensitive phospholipid species to the pyrethroid action. Significant decrease in membrane lipid peroxidation and enhanced levels of nitrite and nitrate in plasma and erythrocyte indicate that increased generation and availability of nitric oxide might have rendered tolerance to erythrocyte membrane by protecting the cells from haemolysis. Increased NO(2) and NO(3) may be due to increased activity of nitric oxide synthase (NOS) and/or expression of isoforms of NOS. A possible involvement of free radical scavenging and antioxidant effects of nitric oxide might have contributed to the observed decrease in lipid peroxidation in the present study.

Gluconeogenesis and glycogenolysis in fluoride-treated rats.

Intraperitonial administration of 10 mg fluoride (NaF)/kg body weight resulted in hyperglycemia in rats. Role of gluconeogenesis and glycogenolysis in this hyperglycemic response was evaluated. Results of the study indicate that the fluoride induced hyperglycemia is mainly due to increased hepatic glycogenolysis.