Protective effects of histone deacetylase inhibitor vorinostat on cisplatin nephrotoxicity in rats

Aim: In this study, we aimed to investigate the effect of vorinostat -histonedeacetylase inhibitor-on cisplatin-induced nephrotoxicity in rats.Material and Method: 32 male Sprague-Dawley rats were divided into 4 groups.1.Control group, 2.Cisplatin group, 3.Vorinostat+Cisplatin group and 4.Vorinostatgroup. A single dose of i.p. saline was given to the first group. In the second group, asingle dose of cisplatin (5 mg/kg i.p. ) was given. In the third group, two doses of50mg/kg vorinostat was injected i.p. with a 24 hours interval and 6 hours after thelast dose of vorinostat, a single dose of 5 mg/kg i.p. cisplatin was given. In the forthgroup, two doses of 50mg/kg vorinostat was injected i.p. with a 24 hours interval. Inall groups, 5 days after the last doses rats were anesthetized and with a laparotomyleft kidneys were isolated and perfused via renal artery by Langendorff system andused for perfusion pressure measurement. Right kidneys were isolated forhistopathological evaluation, Western-Blot analysis (TNF-alpha, p21, PUMA-alpha)and MDA measurements. Blood was drawn by cardiac puncture to measure serumurea and creatinine consantration.Results: Perfusion pressures, serum urea and creatinine levels, TNF-alpha, p21 andPUMA-alpha and MDA levels were found to be significantly higher in the Cisplatin2 group compared to the Control group and this was evaluated for nephrotoxicity. Inaddition, histopathological changes such as tubular atrophy, epithelial desquamation,debris, necrotic material in the tubular lumen and lymphocyte density in theinterstitial tissue supported nephrotoxicity. All these parameters significantlydecreased in the Vorinostat+Cisplatin group compared to the Cisplatin group.Conclusions: As a result it was observed that vorinostat has protective effects on cisplatin-induced nephrotoxicity.