Sirolimus attenuates reduced-size liver ischemia-reperfusion injury but impairs liver regeneration in rats

Abstract

Background: Evidence has suggested that immunosuppressive drugs impact ischemia-reperfusion injury.

Aims: The purpose of the present study was to evaluate the effect of sirolimus on hepatic injury and regeneration in a rat reduced-size liver ischemia-reperfusion model.

Methods: Using a newly developed rat reduced-size liver ischemia-reperfusion injury model, the effects of sirolimus were evaluated by assessing liver cell apoptosis and aspartate aminotransferase, myeloperoxidase, and malondialdehyde levels. In addition, liver regeneration after sirolimus treatment was evaluated by measuring liver weight resumption and by the histological examination of bromodeoxyuridine and proliferating cell nuclear antigen expression.

Results: Sirolimus significantly decreased liver cell apoptosis as well as tissue myeloperoxidase and malondialdehyde levels, but impaired postischemic liver regeneration. Ischemia-reperfusion-induced elevation of aspartate aminotransferase serum levels was significantly decreased by sirolimus.

Conclusions: Despite an impairment of postischemic liver proliferation, sirolimus demonstrated beneficial amelioration of ischemia-reperfusion-induced liver injury in a reduced-size liver model in rats.