Inhibition of PARP activation by enalapril is crucial for its renoprotective effect in cisplatin-induced nephrotoxicity in rats.

Inhibition of PARP activation by enalapril is crucial for its renoprotective effect in cisplatin-induced nephrotoxicity in rats. Free Radic Res. 2016 Aug 30;:1-31 Authors: Rani N, Bharti S, Tomar A, Dinda AK, Arya DS, Bhatia J Abstract Oxidative-stress induced PARP activation has been recognized to be a main factor in the pathogenesis of cisplatin-induced nephrotoxicity. Accumulating literature has revealed that ACE inhibitors may exert beneficial effect in several disease models via preventing PARP activation. Based on this hypothesis, we have evaluated the renoprotective effect of enalapril, an ACE inhibitor, and its underlying mechanism(s) in cisplatin-induced renal injury in rats. Male Albino Wistar rats were orally administered normal saline or enalapril (10, 20 and 40mg/kg) for 10 days. Nephrotoxicity was induced by a single dose of cisplatin (8mg/kg; i.p.) on the 7(th) day. The animals were thereafter sacrificed on the 11(th) day and both the kidneys were excised and processed for biochemical, histopathological, molecular and immunohistochemical studies. Enalapril (40mg/kg) significantly prevented cisplatin-induced renal dysfunction. In comparison to cisplatin treated group, the elevation of BUN and creatinine levels were significantly less in this group. This improvement in kidney injury markers was well substantiated with reduced PARP expression along with phosphorylation of MAPKs including JNK/ERK/p38. Enalapril, in a dose ...
Source: Free Radical Research - Category: Research Tags: Free Radic Res Source Type: research