Benzbromarone mitigates cisplatin nephrotoxicity through enhanced peroxisome proliferator-activated receptor-alpha (PPAR-α) expression

Research Abstract

Key findings: Benzbromarone improved kidney function, that was evidenced by reduced serum creatinine and blood urea nitrogen to nearly the half, compared to the group administered cisplatin alone. The protein expression of PPAR-α was enhanced with benzbromarone treatment, along with a considerable suppression of oxidative stress as benzbromarone reduced mRNA expression of NADPH oxidase, while increased the anti-oxidant HO-1 protein expression through enhancing Nrf2. Besides, it displayed a marked anti-inflammatory effect via suppression of p38 MAPK/NF-κB p65 signaling pathway and its downstream targets. Moreover, benzbromarone retarded apoptosis through reducing the pro-apoptotic (Bax) and enhancing the anti-apoptotic (Bcl-2) protein expressions. The protective effects of benzbromarone were also confirmed by histopathological results.

Research Keywords

Cisplatin nephrotoxicity; Benzbromarone; PPAR-α expression; Nrf2/HO-1; p38 MAPK/NF-κB p65; Bax/Bcl-2