Entacapone scavenges peroxynitrite and protects against kidney and liver injuries induced by renal ischemia/reperfusion in rats

Background Acute kidney injury (AKI), secondary to renal ischemia/reperfusion (I/R), is a serious problem associated with high mortality. The pathophysiology of AKI after renal I/R involves peroxynitrite production; hence, scavenging this metabolite may rescue AKI. Entacapone is a catechol-O-methyl transferase (COMT) inhibitor which elicits antioxidant activity by scavenging peroxynitrite. Therefore, we hypothesized that the peroxynitrite scavenging activity of entacopone protects against AKI after renal I/R injury in rats. Methods Male Wistar rats were given either entacapone or a well-known peroxynitrite scavenger (FeTPPS) daily for 10 days before I/R procedures. I/R was induced by occluding both renal pedicles for 45 min followed by reperfusion for 24 h. Results Pre-treatment with either entacapone or FeTPPS improved renal function as indicated by a significant reduction in serum creatinine and urea when compared to I/R group (P < 0.05). I/R injury increased renal levels of NO (4-folds, P < 0.05), iNOS (4-folds, P < 0.05), and 3-nitrotyrosine (5-folds, P < 0.05) compared to sham control. These effects were abrogated in animals pre-treated with entacapone or FeTPPS before being subjected to I/R (P < 0.05). In addition, entacapone or FeTPPS significantly inhibited I/R-induced elevation in renal TNF-alpha levels (78% and 58%, respectively) and caspase-3 activity (72% and 56%, respectively) indicating the reduction of both inflammation and apoptosis in the kidney (P < 0.05). The two drugs also improved kidney and liver functions in rats with renal I/R injury. Conclusion Our study showed that entacapone and FeTPPS protected against AKI and remote liver damage associated with renal I/R and this effect might be due to scavenging peroxynitrite and reducing nitrosative stress.