title: Chemopreventive efficacy of hesperidin against chemically induced nephrotoxicity and renal carcinogenesis via amelioration of oxidative stress and modulation of multiple molecular pathways.
abstract: In the present study, chemopreventive efficacy of hesperidin was evaluated against ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and carcinogenesis in wistar rats. Nephrotoxicity was induced by single intraperitoneal injection of Fe-NTA (9 mg Fe/kg b.wt). Renal cancer was initiated by the administration of N-nitrosodiethylamine (DEN 200mg/kg b.wt ip) and promoted by Fe-NTA (9 mg Fe/kg b.wt ip) twice weekly for 16 weeks. Efficacy of hesperidin against Fe-NTA-induced nephrotoxicity was assessed in terms of biochemical estimation of antioxidant enzyme activities viz. reduced renal GSH, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, catalase, superoxide dismutase and renal toxicity markers (BUN, Creatinine, KIM-1). Administration of Fe-NTA significantly depleted antioxidant renal armory, enhanced renal lipid peroxidation as well as the levels of BUN, creatinine and KIM-1. However, simultaneous pretreatment of hesperidin restored their levels in a dose dependent manner. Expression of apoptotic markers caspase-3, caspase-9, bax, bcl-2 and proliferative marker PCNA along with inflammatory markers (NFκB, iNOS, TNF-α) were also analysed to assess the chemopreventive potential of hesperidin in two-stage renal carcinogenesis model. Hesperidin was found to induce caspase-3, caspase-9, bax expression and downregulate bcl-2, NFκB, iNOS, TNF-α, PCNA expression. Histopathological findings further revealed hesperidin's chemopreventive efficacy by restoring the renal morphology. Our results provide a powerful evidence suggesting hesperidin to be a potent chemopreventive agent against renal carcinogenesis possibly by virtue of its antioxidant properties and by modulation of multiple molecular pathways.
authors.affiliation: Discipline of Life Sciences, School of Sciences, Indira Gandhi National Open University, Maidan Garhi, New Delhi 110068, India.
authors.forename: Aisha
authors.initials: A
authors.lastname: Siddiqi
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Syed Kazim
authors.initials: SK
authors.lastname: Hasan
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Sana
authors.initials: S
authors.lastname: Nafees
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Summya
authors.initials: S
authors.lastname: Rashid
authors.affiliation: Discipline of Life Sciences, School of Sciences, Indira Gandhi National Open University, Maidan Garhi, New Delhi 110068, India.
authors.forename: Bano
authors.initials: B
authors.lastname: Saidullah
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India. Electronic address: sarwat786@rediffmail.com.
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects*; D002273:Carcinogens / Q000633:toxicity; D002292:Carcinoma, Renal Cell / Q000139:chemically induced / Q000517:prevention & control*; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005290:Ferric Compounds / Q000633:toxicity; D006569:Hesperidin / Q000494:pharmacology*; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002273:Carcinogens; D005290:Ferric Compounds; D006569:Hesperidin; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate
keywords: Apoptosis; Hesperidin; Nephrotoxicity; Oxidative stress; Renal carcinogenesis