Ravichandran Mk

Metformin attenuates blood lipid peroxidation and potentiates antioxidant defense in high fructose-fed rats.

The implication of oxidative stress in the pathology of insulin resistance has been shown recently. We investigated the effect of an insulin sensitizer, metformin, on the plasma lipid peroxidation and antioxidant defense system in the erythrocytes of high fructose fed rats which form an animal model of insulin resistance. The experimental animals were divided into two batches of 12 animals each. The control batch received the control diet, containing starch; the fructose group was given the high fructose diet. At the end of second week these were subdivided into two groups; one was given metformin (50 mg/kg/day in water) by gastric intubation and other group was left untreated. The rats were continued on the same dietary regimen for the next two weeks. Fructose-fed rats showed hyperglycemia, hyperinsulinemia and hypertriglyceridemia at the end of four weeks. Enhanced plasma lipid peroxidation and inadequate cellular antioxidant defense system were observed in them. Administration of metformin was associated with significant normalization of circulating insulin, glucose and triglyceride concentrations. The abnormal triglyceride distribution in the lipoprotein fractions was also ameliorated by metformin therapy. The imbalance between peroxidation and antioxidant defense system was mitigated when fructose-fed rats were treated with metformin. In the control rats, metformin did not affect the parameters studied. Significant positive correlation was obtained between insulin, triglycerides and glucose concentrations with lipid hydroperoxides suggesting that these metabolic variables could influence the lipid peroxide levels in plasma.

Influence of 6-week exercise training on erythrocyte and liver antioxidant defense in hyperinsulinemic rats

High dosage of fructose in rats causes insulin resistance and hyperinsulinemia. This study investigates the effect of physical exercise on oxidant-antioxidant balance in rats fed a high fructose diet, which show characteristic features of insulin resistance. Products of lipid peroxidation and the activity of enzymic antioxidants namely superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase, in red blood cells (RBCs) and liver were assayed. Levels of non-enzymic antioxidants alpha-tocopherol and ascorbic acid and of protein and non-protein thiols were also determined. The levels of lipid peroxides, diene conjugates, lipofuscin and hydroperoxides were significantly higher in the liver of fructose-fed rats. The RBCs showed significantly higher susceptibility to H(2)O(2)-induced stress compared to control rats. Inadequate antioxidant system was noted in high fructose-fed rats. Physical training to these rats reversed the adverse effects, which could be important in alleviating the pathological consequences of insulin resistance.

Renoprotective and blood pressure-lowering effect of dietary soy protein via protein kinase C βII inhibition in a rat model of metabolic syndrome

We studied whether substitution of soy protein for casein can improve insulin sensitivity, lower blood pressure (BP), and inhibit protein kinase C betaII (PKCbetaII) activation in kidney in an acquired model of metabolic syndrome. Adult male rats were fed 4 different diets: (i) starch (60%) and casein (20%) (CCD), (ii) fructose (60%) and casein (20%) (FCD), (iii) fructose (60%) and soy protein (20%) (FSD), and (iv) starch (60%) and soy protein (20%) (CSD). Renal function parameters, BP, pressor mechanisms, PKCbetaII expression, oxidative stress, and renal histology were evaluated after 60 days. FCD rats displayed insulin resistance and significant changes in body weight, kidney weight, urine volume, plasma and urine electrolytes accompanied by significant changes in renal function parameters compared with CCD rats. Elevated BP, plasma angiotensin-converting enzyme (ACE) activity, renal oxidative stress, and reduced nitrite (NO) and kallikrein activity were observed. Western blot analysis revealed enhanced renal expression of membrane-associated PKCbetaII in the FCD group. Histology showed fatty infiltration and thickening of glomeruli while urinary protein profile revealed a 5-fold increase in albumin. Substitution of soy protein for casein improved insulin sensitivity, lowered BP and PKCbetaII activation and restored renal function. Antioxidant action, inhibitory effect on ACE and PKCbetaII activation, and increased availability of kinins and NO could be contributing mechanisms for the benefits of dietary soy protein.

(-) Epigallocatechin Gallate (EGCG) Prevents Lipid Changes and Collagen Abnormalities in Chronic Ethanol-Fed Rats

ABSTRACT The objective of the study is to examine the influence of (-) epigallocatechin gallate (EGCG), a green tea component, on lipid and collagen abnormalities in chronic ethanol-fed rats. Solubility properties, aldehyde content, fluorescence, and peroxidation were analyzed in collagen samples isolated from liver. Chronic alcoholism (6 g/kg/day × 60 days) was associated with fatty liver and collagen accumulation. Significant alterations in the levels of lipids (cholesterol, phospholipids, free fatty acids, and triglycerides) and total collagen were observed in liver. Collagen obtained from ethanol-fed rats showed alterations in solubility properties, increased fluorescence, peroxidation, and aldehyde content. Coadministration of EGCG along with ethanol significantly reduced the levels of liver lipids and collagen, improved the solubility properties of collagen, and caused a reduction in cross-linking as evidenced by a decrease in fluorescence, peroxidation, and aldehyde content. Histology of liver sections of ethanol-fed rats showed accumulation of fat and collagen, which were largely prevented by EGCG administration. The possible mechanisms in the protective action of EGCG in alcoholic liver disease are suggested and discussed.