title: Chrysin suppresses renal carcinogenesis via amelioration of hyperproliferation, oxidative stress and inflammation: plausible role of NF-κB.
abstract: 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.
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Muneeb U
authors.initials: MU
authors.lastname: Rehman
authors.forename: Mir
authors.initials: M
authors.lastname: Tahir
authors.forename: Abdul Quaiyoom
authors.initials: AQ
authors.lastname: Khan
authors.forename: Rehan
authors.initials: R
authors.lastname: Khan
authors.forename: Abdul
authors.initials: A
authors.lastname: Lateef
authors.lastname: Oday-O-Hamiza
authors.forename: Wajhul
authors.initials: W
authors.lastname: Qamar
authors.forename: Farrah
authors.initials: F
authors.lastname: Ali
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
mesh_terms: D000818:Animals; D002273:Carcinogens; D002292:Carcinoma, Renal Cell / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000097:blood; D016207:Cytokines / Q000097:blood; D004052:Diethylnitrosamine; D005290:Ferric Compounds; D005419:Flavonoids / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000097:blood*; D052247:Nitric Oxide Synthase Type II / Q000097:blood; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives; D009955:Ornithine Decarboxylase / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D010865:Pilot Projects; D018809:Proliferating Cell Nuclear Antigen / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002273:Carcinogens; D016207:Cytokines; D005290:Ferric Compounds; D005419:Flavonoids; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; C043561:chrysin; D004052:Diethylnitrosamine; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D009955:Ornithine Decarboxylase; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate