Attenuation of chloroquine-induced renal damage by alpha-lipoic acid: Possible antioxidant mechanism

The toxic effect of chloroquine (CQ) has been attributed to oxidative stress with the consequences of lipid peroxidation. This study investigates the effects of a-lipoic acid (LA) on CQ-induced nephrotoxicity in rats. A single oral administration of CQ (970 mg/kg)-induced nephrotoxicity, manifested biochemically by a significant increase in serum creatinine and blood urea nitrogen concentrations. In addition, renal tissue from CQ-treated rats showed a significant increase in lipid peroxides measured as thiobarbituric acid reactive substances and hydroperoxides, along with significant decrease in nonenzymic antioxidants (vitamin C, vitamin E, and reduced glutathione) and enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase) levels. Oral administration of LA (10, 30, or 100 mg/kg) in different doses for 10 days produced a significant protection against nephrotoxicity induced by CQ. Treatment with LA markedly reduced the elevated lipid peroxidation, restored the depleted renal antioxidant defense system. LA at 100 mg/kg was effective when compared with other doses (10 and 30 mg/kg). This was accompanied by the histopathological observations in kidney tissue. The results suggest that LA ameliorate the lipid peroxidation and the loss of cellular antioxidants, thereby protecting the CQ-induced oxidative damage in kidney.