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Anti‐carcinogenic effect of hesperidin against renal cell carcinoma by targeting COX‐2/PGE2 pathway in Wistar rats

Siddiqi, Aisha, Saidullah, Bano, Sultana, Sarwat
Environmental toxicology 2018 v.33 no.10 pp. 1069-1077
anticarcinogenic activity, antioxidant activity, antioxidants, carcinogenesis, catalase, chemoprevention, creatinine, hesperidin, histology, iron, kidneys, laboratory animals, lipid peroxidation, oxidative stress, rats, renal cell carcinoma, renal function, superoxide dismutase, vascular endothelial growth factors
The present study was designed to evaluate the protective effects of hesperidin, a flavonoid on DEN initiated and Fe‐NTA promoted renal carcinogenesis in Wistar rats. Renal cancer was initiated by a single i.p. injection of DEN (200 mg/kg b.wt.) and promoted with Fe‐NTA (9 mg Fe/kg b.wt. i.p.) twice a week for 16 weeks. Rats were simultaneously administered with hesperidin (100 and 200 mg/kg b.wt.) for 16 consecutive weeks. The chemopreventive effect of hesperidin was assessed in terms of antioxidant activities, renal function, PGE2 level, and the expressions of COX‐2 and VEGF. Hesperidin decreased the DEN and Fe‐NTA induced lipid peroxidation, improved the renal function (by decreasing the levels of BUN, creatinine, and KIM‐1) and restored the renal antioxidant armory (GSH, GPx, GR, SOD, and catalase). Hesperidin was also found to decrease the level of PGE2 and downregulate the expressions of COX‐2 and VEGF. Histological findings further revealed the protective effects of hesperidin against DEN and Fe‐NTA induced kidney damage. The result of our present findings suggest that hesperidin may be a promising modulator in preventing renal cancer possibly by virtue of its ability to alleviate oxidative stress and inhibit COX‐2/PGE2 pathway.