L-carnitine ameliorates l-asparaginase-induced acute liver toxicity in steatotic rat livers

Abstract

Background: Chemotherapy with L-asparaginase is associated with hepatotoxicity resulting in organ dysfunction in patients with preexisting liver disorders. This study investigated the protective effect of L-carnitine during chemotherapy in a steatotic rat liver model. Methods: Livers from nonsteatotic and steatotic rats were tested in an isolated liver reperfusion model adding L-asparaginase and L-carnitine to the reperfusate. Portal venous pressure (PVP), hepatic oxygen consumption, aspartate aminotransferase, lactate dehydrogenase, glutamate dehydrogenase and α-glutathione S-transferase levels were assessed. Further histopathological analysis was performed and cytotoxicity was verified in vitro. Results:L-Asparaginase induced toxicity in fatty livers whereas low toxicity was observed in normal livers. L-Carnitine induced a decline in PVP and oxygen consumption, and reduced parenchymal and mitochondrial damage in fatty livers. Cytotoxicity of L-asparaginase was not impaired by the presence of L-carnitine. Conclusions: Our study emphasizes the potential of L-carnitine to reduce L-asparaginase-induced hepatotoxicity in patients with preexisting liver disorders. © 2013 S. Karger AG, Basel.