Abstract Title:

Chemopreventive efficacy of hesperidin against chemically induced nephrotoxicity and renal carcinogenesis via amelioration of oxidative stress and modulation of multiple molecular pathways.

Abstract Source:

Exp Mol Pathol. 2015 Dec ;99(3):641-53. Epub 2015 Nov 10. PMID: 26551080

Abstract Author(s):

Aisha Siddiqi, Syed Kazim Hasan, Sana Nafees, Summya Rashid, Bano Saidullah, Sarwat Sultana

Article Affiliation:

Aisha Siddiqi

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 (9mg 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 (9mg Fe/kg b.wt ip) twice weekly for 16weeks. 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.

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