左旋肉碱可改善脂肪变性大鼠肝脏中门冬酰胺酶诱导的急性肝毒性。
L-carnitine ameliorates L-asparaginase-induced acute liver toxicity in steatotic rat livers.
机构信息
Institute for Laboratory Animal Science, University Hospital, RWTH Aachen University, Aachen, Germany.
出版信息
Chemotherapy. 2013;59(3):167-75. doi: 10.1159/000353402. Epub 2013 Oct 31.
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.
背景
含左旋门冬酰胺酶的化疗会导致肝毒性，使原有肝脏疾病的患者发生器官功能障碍。本研究旨在探讨左旋肉碱在脂肪性肝模型中对化疗药物所致肝损伤的保护作用。
方法
采用离体肝脏再灌注模型，分别在含或不含左旋门冬酰胺酶和左旋肉碱的再灌注液中检测非脂肪性和脂肪性大鼠的肝脏。评估门静脉压力（PVP）、肝氧耗、天冬氨酸氨基转移酶、乳酸脱氢酶、谷氨酸脱氢酶和α-谷胱甘肽 S-转移酶水平。进一步进行组织病理学分析，并在体外验证细胞毒性。
结果
左旋门冬酰胺酶在脂肪性肝脏中诱导了毒性，而在正常肝脏中观察到的毒性较低。左旋肉碱可降低 PVP 和氧耗，并减轻脂肪性肝脏的实质和线粒体损伤。左旋肉碱的存在并未损害左旋门冬酰胺酶的细胞毒性。
结论
本研究强调了左旋肉碱在降低原有肝脏疾病患者的左旋门冬酰胺酶诱导肝毒性方面的潜力。
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