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.