Effects of asparaginases and L-carnitine on Western-diet-induced hepatosteatosis in mice

<ns4:p> <ns4:bold>Abstract</ns4:bold> </ns4:p> <ns4:p> <ns4:bold>Background:</ns4:bold> Asparaginases are common chemotherapeutic agents used for the treatment of acute lymphoblastic leukemia as a single or combinational therapy. Accompanying hepatotoxicity makes its use in elderly patients with pre-conditions, as obesity or other hepatopathies, difficult. Various hepatoprotective compounds like, L-carnitine, are discussed to ameliorate the induced hepatotoxicity. </ns4:p> <ns4:p> <ns4:bold>Methods:</ns4:bold> Here we aimed to establish a mouse model to study the effect of asparaginases (L-asparaginase and Oncaspar) and L-carnitine on Western-diet-induced hepatosteatosis in mice. Dose-escalation studies were performed to analyze asparaginases induced hepatotoxicity in C57BL/6 mice with normal or fatty livers. Subsequently, the effect of L-carnitine to improve the induced toxicity was tested. </ns4:p> <ns4:p> <ns4:bold>Results:</ns4:bold> Our results showed mild-to-moderate hepatotoxic effects while the Western-diet induced a higher degree of vacuolization and hepatocyte damage in liver tissue. Testing of L-carnitine in the established models did not show any protective effect on the toxicity or impairment of the efficacy of asparaginases. </ns4:p> <ns4:p> <ns4:bold>Conclusion:</ns4:bold> The here established models were able to demonstrate the asparaginase-induced hepatotoxic effects which were enhanced by the Western-diet. However, to test potential ameliorating drugs, the models might need some improvements. </ns4:p>