Involvement of oxidative stress in tri-ortho-cresyl phosphate-induced liver injury in male mice
Involvement of oxidative stress in tri-ortho-cresyl phosphate-induced liver injury in male mice
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氧化应激参与磷酸三邻甲苯酯诱导的雄性小鼠肝损伤
DOI：
10.1177/0960327115621363
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发表时间：
2016-10-01
影响因子：
2.8
通讯作者：
Chen, J. X.
中科院分区：
文献类型：
--
作者：
Xu, L. L.;Long, C. Y.;Chen, J. X.
磷酸三邻甲苯酯（TOCP）在工业上被广泛用作增塑剂、塑料软化剂和阻燃剂，据报道在动物中具有延迟神经毒性和生殖毒性。然而，TOCP是否引起肝损伤仍是一个谜。在本研究中，雄性小鼠经口给予不同浓度的TOCP（100、200或400 mg/kg/天），持续28天。组织学检查显示TOCP导致严重的肝细胞损伤。此外，TOCP给药诱导小鼠血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平显著升高。TOCP染毒后，小鼠肝脏中丙二醛（MDA）含量显著升高，谷胱甘肽（GSH）含量及抗氧化酶超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）活性显著降低。TOCP以剂量依赖性方式抑制小鼠肝癌Hepa 1-6细胞的活力。同时，TOCP可显著增加细胞内MDA含量，抑制细胞内GSH含量及SOD、GSH-PX活性。氧化应激可显著抑制Hepa 1-6细胞的活力，而N-乙酰-L-半胱氨酸抑制氧化应激可在一定程度上挽救TOCP抑制的细胞活力。总之，氧化应激可能参与TOCP诱导的雄性小鼠肝细胞损伤。
Tri-ortho-cresyl phosphate (TOCP) has been widely used as plasticizers, plastic softeners, and flame retardants in industry and reported to have delayed neurotoxicity and reproductive toxicology in animals. However, it remains to be elusive whether TOCP induces liver injury. In this study, male mice were orally administered different concentrations of TOCP (100, 200, or 400 mg/kg/day) for 28 days. Histological examination showed that TOCP led to serious hepatocellular injury. In addition, administration of TOCP induced a marked elevation in the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice. The content of malondialdehyde (MDA) was increased significantly in the liver after the mice were treated with TOCP; while there was a dramatic decrease in the content of glutathione (GSH) and the activities of antioxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). TOCP inhibited viability of mouse liver cancer Hepa 1-6 cells in a dose-dependent manner. Meanwhile, TOCP significantly increased MDA content and inhibited GSH content and the activities of SOD and GSH-PX in the cells, respectively. Oxidative stress dramatically inhibited viability of Hepa 1-6 cells; while inhibition of oxidative stress by N-acetyl-l-cysteine could rescue the cell viability inhibited by TOCP to a certain extent. In summary, oxidative stress might be involved in TOCP-induced hepatocellular injury in male mice.