Tropisetron Protects Against Acetaminophen-Induced Liver Injury via Suppressing Hepatic Oxidative Stress and Modulating the Activation of JNK/ERK MAPK Pathways.
Tropisetron Protects Against Acetaminophen-Induced Liver Injury via Suppressing Hepatic Oxidative Stress and Modulating the Activation of JNK/ERK MAPK Pathways.
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DOI：
10.1155/2016/1952947
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发表时间：
2016
影响因子：
--
通讯作者：
Yu HP
中科院分区：
文献类型：
--
作者：
Liu FC;Lee HC;Liao CC;Li AH;Yu HP
目标。目的探讨托司司琼对对乙酰氨基酚（APAP-）所致小鼠肝损伤的保护作用。方法。C57BL/6雄性小鼠在给予对乙酰氨基酚（300 mg/kg）肝毒性剂量前30分钟腹腔注射托哌司琼（0.3 ~ 10 mg/kg）。APAP中毒20 h后，检测血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）水平、肝髓过氧化物酶（MPO）、丙二醛（MDA）、谷胱甘肽（GSH）、超氧化物歧化酶（SOD）活性及肝脏组织病理学变化。western blotting检测MAP激酶。结果。我们的研究结果表明，托烷司琼预处理显著降低apap诱导的肝毒性小鼠肝酶ALT水平、肝MPO活性和肝细胞坏死的急性升高，并呈剂量依赖性（0.3-10 mg/kg）。托匹司琼（1和3 mg/kg）抑制apap诱导的肝脂质过氧化表达，减轻GSH和SOD的消耗。托司司琼还能减弱APAP引起的c- jun - nh2末端蛋白激酶（JNK）和细胞外信号调节激酶（ERK）的磷酸化。结论。我们的数据表明，托司司琼的肝保护作用部分与抗氧化剂有关，抗氧化剂通过JNK和ERK途径介导对乙酰氨基酚诱导的小鼠肝损伤。
Objectives. To investigate the protective effects of tropisetron on acetaminophen- (APAP-) induced liver injury in a mice model. Methods. C57BL/6 male mice were given tropisetron (0.3 to 10 mg/kg) 30 minutes before a hepatotoxic dose of acetaminophen (300 mg/kg) intraperitoneally. Twenty hours after APAP intoxication, sera alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activities, and liver histopathological changes were examined. The MAP kinases were also detected by western blotting. Results. Our results showed that tropisetron pretreatment significantly attenuated the acute elevations of the liver enzyme ALT level, hepatic MPO activity, and hepatocytes necrosis in a dose-dependent manner (0.3–10 mg/kg) in APAP-induced hepatotoxicity mice. Tropisetron (1 and 3 mg/kg) suppressed APAP-induced hepatic lipid peroxidation expression and alleviated GSH and SOD depletion. Administration of tropisetron also attenuated the phosphorylation of c-Jun-NH2-terminal protein kinase (JNK) and extracellular signal-regulated kinase (ERK) caused by APAP. Conclusion. Our data demonstrated that tropisetron's hepatoprotective effect was in part correlated with the antioxidant, which were mediated via JNK and ERK pathways on acetaminophen-induced liver injury in mice.
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影响因子：
3.8
作者：
Du, Kuo;Williams, C. David;McGill, Mitchell R.;Jaeschke, Hartmut
通讯作者：
Jaeschke, Hartmut
影响因子：
6
作者：
Bhushan, Bharat;Borude, Prachi;Apte, Udayan
通讯作者：
Apte, Udayan
氧化应激生物标志物：活细胞中外源性和内源性丙二醛的荧光探针。
影响因子：
7.4
作者：
Chen, Jin;Zeng, Lingyu;Liu, Zhihong
通讯作者：
Liu, Zhihong
影响因子：
3.8
作者：
McGill, Mitchell R.;Lebofsky, Margitta;Norris, Hye-Ryun K.;Slawson, Matthew H.;Bajt, Mary Lynn;Xie, Yuchao;Williams, C. David;Wilkins, Diana G.;Rollins, Douglas E.;Jaeschke, Hartmut
通讯作者：
Jaeschke, Hartmut
DOI：
10.1124/jpet.110.176321
发表时间：
2011-04-01
影响因子：
3.5
作者：
Agarwal, Rakhee;MacMillan-Crow, Lee Ann;Hinson, Jack A.
通讯作者：
Hinson, Jack A.