Protection of Hesperidin against Methotrexate- Induced Nephrotoxicity may be Mediated by Nrf2/HO-1 Pathway

Abstract: Background: Methotrexate (MTX), a successfully used chemotherapeutic in the treatment of various malignancies and autoimmune diseases, might cause severe nephrotoxicity. Here, we aimed at investigating possible nephroprotective effects hesperidin (HES), flavanone present citrus fruits, against MTX-induced toxicity. Methods: Rats were divided into control, HES, MTX, MTX/HES groups, where HES was administered dose 100 mg/kg/day orally for 8 days MTX single i.p. 20 mg/kg on day 5 experiment. Results: Pretreatment with significantly improved MTXinduced deteriorated kidney function structure, as well reversed renal tumor necrosis factor (TNF)-α level caspase 3 expression. upregulated breast cancer resistance protein (BCRP); an efflux transporter that extrudes from kidney. Unfortunately, did not show further increase BCRP expression but rather showed downregulation. also caused downregulation nuclear erythroid 2-related 2 (Nrf2) hemeoxygenase-1 (HO-1) expressions, whereas effect Nrf2/HO-1. Conclusion: conferred protection MTX-mediated nephrotoxicity, least part via anti-inflammatory anti-apoptotic mechanisms. Nrf2/HO-1 pathway, BCRP, may have role HES-induced nephroprotection Key words: Methotrexate, Hesperidin, Nrf2, HO-1, TNF-α, Caspase 3, BCRP.