Treatment with aliskiren ameliorates tacrolimus-induced nephrotoxicity in rats

Abstract

Introduction: Tacrolimus is frequently used as immunosuppressive agent in organ transplantation but its clinical use is limited due to its marked nephrotoxicity.

Materials and methods: Male Wistar albino rats weighing 150-200 g (10-12 weeks old) were used. Animals were divided into four groups. Group 1 served as control group and received normal saline, group 2 served as toxic group and received 2 mg/kg tacrolimus i.p., group 3 served as treatment group and received 2 mg/kg tacrolimus i.p. followed by 2 mg/kg aliskiren orally and group 4 served as drug per se group and received 2 mg/kg aliskiren orally. Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically.

Results: Treatment with aliskiren decreased the tacrolimus-induced changes in biochemical markers of nephrotoxicity such as blood urea nitrogen and creatinine. Aliskiren also attenuated the effects of tacrolimus on oxidative stress parameters such as malondialdehyde, reduced glutathione and catalase. Histopathological and ultrastructural studies showed that aliskiren attenuated tacrolimus-induced renal damage.

Conclusion: These results suggest that aliskiren has protective effects against tacrolimus-induced nephrotoxicity; implying that renin inhibitor may counteract nephrotic syndrome associated with immunosuppressant use.

Keywords: Aliskiren; nephrotoxicity; renin inhibitor; tacrolimus.