Protective effect of ellagic acid against TCDD-induced renal oxidative stress: Modulation of CYP1A1 activity and antioxidant defense mechanisms

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) belongs to toxicologically important class of poly halogenated aromatic hydrocarbons and produce wide variety of adverse effects in humans. The present study investigated the protective effect of ellagic acid, a natural polyphenolic compound against TCDD-induced nephrotoxicity in Wistar rats. TCDD-induced nephrotoxicity was reflected in marked changes in the histology of kidney, increase in levels of kidney markers (serum urea, serum creatinine) and lipid peroxides. A significant increase in activity of phase I enzyme CYP1A1 with concomitant decline in the activities of phase II enzymes [non-enzymic antioxidant and various enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase] was also observed. In addition, TCDD treated rats showed alterations in ATPase enzyme activities such as Na(+) K(+)-ATPase, Mg(2+) ATPase and Ca(2+) ATPase. Oral pre-treatment with ellagic acid prevented TCDD-induced alterations in levels of kidney markers. Ellagic acid pre-treatment significantly counteracted TCDD-induced oxidative stress by decreasing CYP1A1 activity and enhancing the antioxidant status. Furthermore, ellagic acid restored TCDD-induced histopathological changes and alterations in ATPase enzyme activities. The results of the present study show that significant protective effect rendered by ellagic acid against TCDD-induced nephrotoxicity might be attributed to its antioxidant potential.