301 - Chrysin Suppresses Development of Precancerous Lesions in Kidneys by Regulation of Oxidative Stress, Inflammation, Hyperproliferation and Apoptosis in Murine Model

Abstract

Chrysin (CH) is a natural compound which belongs to flavonoid family and possesses diverse pharmacological activities like anti-inflammatory, anti-oxidant and anti-cancer. It is found in many plants, honey and propolis. In the present study, we investigated the chemopreventive efficacy of CH against N-nitrosodiethylamine (DEN) initiated and Fe-NTA induced renal carcinogenesis and its role in regulating oxidative injury, histopathological alterations, ultra structural changes, inflammation, hyper proliferation, tumor incidences and apoptosis in the kidneys of Wistar rats. Renal cancer was initiated by single intraperitoneal (i.p.) injection of DEN (200mg/kg b.w) and promoted by twice weekly injection of ferric nitrilotriacetate (Fe-NTA) 9 mg Fe/kg bw for 16 weeks. CH attenuated oxidative injury induced by DEN and Fe-NTA administration. CH supplementation suppressed the development of renal carcinogenesis induced by DEN initiation and Fe-NTA promotion via down regulation of cell proliferation marker like PCNA; tumor incidences and inflammatory mediators like TNF-α, IL-6, NFkB, Cox-2, iNOS. CH up regulated intrinsic apoptotic pathway proteins like bax, bcl-2, caspase-9 and caspase-3 triggering apoptosis. Histopathological and ultra structural alterations further supported our previous findings. Henceforth our results provide a powerful evidence for the chemopreventive efficacy of CH against chemically induced renal carcinogenesis possibly by modulation of multiple molecular pathways.