الفهرس 
Title : Evaluation of the potential renoprotective effect of vitamin D and/or retinoic acid on cisplatin-induced
CONTENTSOnly 14 pages are availabe for public view
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Abstract
Background: Although the modulation of vitamin D receptor (VDR), retinoid X receptor (RXR) and endothelin A receptor (ETAR) have been reported previously to offer renoprotection against cisplatin-induced nephrotoxicity and other models of renal injury, the possible interaction between the ET-1, vitamin D and retinoic acid pathways remains obscure. Methods: To fulfil this goal, BQ-123 (selective ETAR blocker), all-trans retinoic acid (ATRA) (RXR agonist; 1 mg/kg) and alfacalcidol (ALF) (vitamin D3 analogue; 50 ng/kg), were used either alone or in combination against a cisplatin-induced (6 mg/kg, i.p) nephrotoxic model in male Sprague{u2013}Dawley rats. Both vitamins were gavaged orally 5 days before and 14 days after cisplatin administration. Meanwhile, BQ-123 (1 mg/kg/day, i.p) was injected one hr before cisplatin and one day after. Nephrotoxicity was evaluated 96 hrs and 14 days following cisplatin administration. Results: BQ-123, ALF and ATRA have counteracted cisplatin-induced nephrotoxic changes. They reduced serum creatinine and urea, renal contents of endothelin-1 (ET-1), tumor necrosis factor-alpha, transforming growth factor-beta1, phosphorylated nuclear factor-kappa-B, and caspase-3 activity. Besides, all regimens downregulated ETAR expression and improved the cisplatin-induced {u2018}acute tubular necrosis{u2019} pattern. Meanwhile, treatments have upregulated VDR, RXR-Ü and endothelin B receptor (ETBR) expression, except BQ-123, which did not affect ETBR. The effect of the combination regimens surpassed that of each agent alone