Diosmin protects against TCE (trichloroethylene) induced renal injury in Wistar rats: Plausible role of p53, Bax and caspases

Abstract

Diosmin (DM) is a naturally occurring flavone and has been found to possess numerous therapeutic properties. In this study, we used DM as a protective agent against the nephrotoxic effects of the environmental toxicant trichloroethylene (TCE). Male Wistar rats were divided into five groups (I–V, n 6). Groups II, III and IV received an oral administration of TCE at a dose of 1000 mg/kg body weight for twenty consecutive days. The animals in groups II and III received an oral treatment of DM at doses of 20 and 40 mg/kg body weight, respectively, for twenty consecutive days, while groups I and V were given maize oil (5 ml/kg body weight and DM 40 mg/kg body weight, respectively) for 20 d. The protective effects of DM on TCE-induced oxidative stress and caspase-dependent apoptosis were investigated by assaying oxidative stress biomarkers, lipid peroxidation (LPO), serum toxicity markers, alkaline unwinding assay, caspase-3, -7 and -9, Bax and p53 expression. Oral administration of TCE in rats enhanced renal LPO, depleted glutathione content and antioxidant enzymes, induced DNA strand breaks (P,0·001), modulated the expression of Bax and p53 protein and induced the expression of caspase-3, -7 and -9. Co-treatment with DM prevented oxidative stress by restoring the levels of antioxidant enzymes; furthermore, a significant dose-dependent decrease in DNA disintegration and kidney toxicity markers such as blood urea N, creatinine, lactate dehydrogenase and kidney injury molecule-1 was observed. DM also effectively decreased the TCE-induced up-regulation of Bax and p53. Data from the present study establish the protective role of DM against TCE-induced renal damage.