Protective effect of lisinopril on hepatic ischemia/reperfusion injury in rats

Abstract

Objective: Ischemia/reperfusion (I/R) injury plays a key role in the pathogenesis of hepatic failure in several clinical settings such as liver resection or transplantation. Lisinopril, a widely prescribed drug for various cardiovascular conditions, has been reported to have diverse pharmacological properties. The aim of this study, therefore, was to evaluate a potential protective effect of lisinopril on hepatic I/R injury in rats.

Materials and methods: In anesthetized rats, partial hepatic ischemia was applied for one hour followed by two hours reperfusion. Biochemical analysis of serum and hepatic tissue was done. Hepatic tissue was also subjected to electron microscopy.

Results: Pre-ischemic treatment with lisinopril (10 mg/kg) exerted protection against I/R-induced hepatocellular injury as evident by significant decrease in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin levels, along with hepatic lipid peroxidation, expressed as malondialdehyde content, with a concurrent increase in hepatic nitric oxide content as compared to I/R group. The electron microscopic examination indicated that lisinopril can effectively protect against hepatic I/R injury.

Conclusion: Lisinopril provides a protection against hepatic I/R injury in rats. The protective effect is associated with reduction of oxidative stress-induced lipid peroxidation level and enhancement of nitric oxide availability.

Keywords: Ischemia/reperfusion; lisinopril; liver.

Figure 1

Effect of lisinopril on hepatic a) malondialdehyde and b) total nitrite/nitrate levels after two hours of reperfusion. Data shown are mean ± SEM of six rats. *,Δ Significantly different from sham and ischemia/reperfusion (I/R) untreated groups, respectively, at P < 0.05 (ANOVA)

Figure 2

Electron micrographs depict the ultra structural changes in hepatocytes of a) sham, b,c) ischemia/reperfusion (I/R)-untreated and d) lisinopril-treated groups. Pretreatment of rats with lisinopril alleviated the deleterious effects of I/R