chrysin and Kidney-Neoplasms

Chrysin (CH) is natural, biologically active compound, belongs to flavoniod family and possesses diverse pharmacological activities as 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 precancerous lesions and its role in regulating oxidative injury, hyperproliferation, tumor incidences, histopathological alterations, inflammation, and apoptosis in the kidneys of Wistar rats. Renal cancer was initiated by single intraperitoneal (i.p.) injection of DEN (200 mg/kg bw) and promoted by twice weekly injection of ferric nitrilotriacetate (Fe-NTA) 9 mg Fe/kg bw for 16 weeks. CH attenuated Fe-NTA enhanced renal lipid peroxidation, serum toxicity markers and restored renal anti oxidant armory significantly. CH supplementation suppressed the development of precancerous lesions via down regulation of cell proliferation marker like PCNA; inflammatory mediators like TNF-α, IL-6, NFkB, COX-2, iNOS; tumor incidences. CH up regulated intrinsic apoptotic pathway proteins like bax, caspase-9 and caspase-3 along with down regulation of Bcl-2 triggering apoptosis. Histopathological and ultra structural alterations further confirmed biochemical and immunohistochemical results. These results provide powerful evidence for the chemopreventive efficacy of CH against chemically induced renal carcinogenesis possibly by modulation of multiple molecular pathways.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Apoptosis; Carcinogenesis; Cell Proliferation; Ferric Compounds; Flavonoids; Gene Expression Regulation, Neoplastic; Inflammation; Kidney; Kidney Neoplasms; Lipid Peroxidation; Male; Nitrilotriacetic Acid; Oxidative Stress; Precancerous Conditions; Rats; Rats, Wistar; Up-Regulation

Flavonoid family is a rich source of polyphenolic compounds and hence possess strong antioxidant and anti inflammatory properties. The aim of this study was to determine the efficacy of chrysin; a bio-active flavonoid as an anticancer agent. Renal cancer was initiated by single intraperitoneal (i.p.) injection of N-nitrosodiethylamine (DEN 200 mg/kg BW body weight) and promoted by twice weekly administration of ferric nitrilotriacetate (Fe-NTA) 9 mg Fe/kg BW for 16 wk. In the present study, we report the chemopreventive effects of chrysin against (Fe-NTA) induced renal oxidative stress, inflammation, hyperproliferative response, and two-stage renal carcinogenesis. To ascertain the molecular mechanism implicated in the antitumor promoting activity of chrysin, its effect was investigated on markers of tumor promotion and inflammation: ornithine decarboxylase (ODC) activity, proliferating cell nuclear antigen (PCNA), inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) expression, and on levels of proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E(2) (PGE(2)). Pretreatment of animals with chrysin at both doses (20 and 40 mg/kg body weight) markedly inhibited all. Further, Fe-NTA enhances renal lipid peroxidation, with concomitant reduction in reduced glutathione content (GSH), antioxidant enzymes, and phase II metabolizing enzymes. It induces serum toxicity markers, viz., blood urea nitrogen (BUN), creatinine and lactate dehydrogenase (LDH). Prophylactic treatment of animals with chrysin before the administration of Fe-NTA was effective in modulating oxidative and renal injury markers and resulted in the diminution of Fe-NTA mediated injury. These results suggest chrysin as an effective chemopreventive agent having the capability to obstruct DEN initiated and Fe-NTA promoted renal cancer in the rat model.

Topics: Animals; Carcinogens; Carcinoma, Renal Cell; Cell Proliferation; Cyclooxygenase 2; Cytokines; Diethylnitrosamine; Ferric Compounds; Flavonoids; Kidney Neoplasms; Male; NF-kappa B; Nitric Oxide Synthase Type II; Nitrilotriacetic Acid; Ornithine Decarboxylase; Oxidative Stress; Pilot Projects; Proliferating Cell Nuclear Antigen; Random Allocation; Rats; Rats, Wistar