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.
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.
Authors: David O Riley; Jenna M Schlefman; Hans Christoph Vitzthum Von Eckstaedt V; Amy L Morris; Michael K Keng; Firas El Chaer Journal: Curr Hematol Malig Rep Date: 2021-05-12 Impact factor: 3.952
Authors: Natasha Kamal; Christopher Koh; Niharika Samala; Robert J Fontana; Andrew Stolz; Francisco Durazo; Paul H Hayashi; Elizabeth Phillips; Tongrong Wang; Jay H Hoofnagle Journal: Hepatol Int Date: 2019-08-07 Impact factor: 6.047
Authors: Hien Anh Nguyen; Ying Su; Jenny Y Zhang; Aleksandar Antanasijevic; Michael Caffrey; Amanda M Schalk; Li Liu; Damiano Rondelli; Annie Oh; Dolores L Mahmud; Maarten C Bosland; Andre Kajdacsy-Balla; Sofie Peirs; Tim Lammens; Veerle Mondelaers; Barbara De Moerloose; Steven Goossens; Michael J Schlicht; Kasim K Kabirov; Alexander V Lyubimov; Bradley J Merrill; Yogen Saunthararajah; Pieter Van Vlierberghe; Arnon Lavie Journal: Cancer Res Date: 2018-01-17 Impact factor: 12.701
Authors: Jessica L Sea; Etan Orgel; Ting Chen; Rebecca L Paszkiewicz; Abigail S Krall; Matthew J Oberley; Linsey Stiles; Steven D Mittelman Journal: Leuk Lymphoma Date: 2019-09-16
Authors: Rachael Schulte; Ashley Hinson; Van Huynh; Erin H Breese; Joanna Pierro; Seth Rotz; Benjamin A Mixon; Jennifer L McNeer; Michael J Burke; Etan Orgel Journal: Cancer Med Date: 2021-09-16 Impact factor: 4.452