糜烂性毒剂氮芥染毒对肝细胞线粒体结构和功能的影响

doi:10.3969/j.issn.1004-616x.2023.02.004

Abstract

Abstract: OBJECTIVE： To investigate effects of the blister agent， nitrogen mustard (HN2)， on mitochondrial structure and function of hepatocytes，based on in vitro and in vivo models. METHODS：In the in vitro model，HepG2 cells were divided into normal control and HN2 exposure groups. The normal control group was treated with serum-free medium containing DMSO (0.1%) for 36 h，and the HN2 exposure group was treated with nitrogen mustard (8 μmol/L). After HN2 treatment for 36 h，cell viability was detected by CCK-8 method， mitochondrial membrane potential by JC-1 probe method， ATP content in cell homogenate and liver tissue by NADPH rate method， and mitochondrial function by Seahorse cell energy metabolism analyzer. Twenty C57BL/6 mice were divided into normal control group and HN2 exposure group. The HN2 exposure group was given a single intraperitoneal injection of nitrogen mustard hydrochloride (2 mg/kg)，and the normal control group was injected with normal saline. Serum and liver tissues were used to measure activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)， and pathological examination of liver tissues and electron microscope observations were performed. Contents of ATP and mitochondrial enzyme complexes I，II and III activities in liver tissues were determined by corresponding kits. RESULTS： In the in vitro model， compared with the normal control group， HN2 exposure decreased cell activity by about 16.2% (P<0.05)， the mitochondrial membrane potential by about 33.2% (P<0.05)， and mitochondrial energy metabolism was significantly abnormal. In the in vivo model，compared with the normal control group，HN2 exposure caused significant increased activities of serum ALT and AST. At the same time， there was large number of inflammatory cell infiltrations into liver tissues accompanied by liver parenchymal cell damage. Mitochondrial morphology was significantly abnormal： manifested as increased number，decreased size，loss or fragmentation of mitochondrial cristae，and significantly decreased activity of mitochondrial enzyme complexes I， II and III (P<0.05). CONCLUSION： HN2 exposure induced mitochondrial damage in hepatocytes and this may be one of the main toxic targets of HN2 poisoning. Results from our study provide new ideas for the prevention and treatment of acute liver injury induced by blister agents such as HN2.

Key words: nitrogen mustard, blister agent, mitochondria, acute liver injury, poisoning

CLC Number:

R827.15

WANG Zhao, LIU Sijia, LIU Jianhao, MA Chengfei, ZHAO Yushun, XU Anqi, AI Duo, QI Yujia, KONG Deqin, LIU Jiangzheng. Effects of blister agent nitrogen mustard exposure on the structure and function of mitochondria in hepatocytes[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(2): 102-108,153.

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Effects of blister agent nitrogen mustard exposure on the structure and function of mitochondria in hepatocytes

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