Absence of Increased Susceptibility to Acetaminophen-Induced Liver Injury in a Diet-Induced NAFLD Mouse Model.
Absence of Increased Susceptibility to Acetaminophen-Induced Liver Injury in a Diet-Induced NAFLD Mouse Model.
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DOI：
10.1177/01926233231171101
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发表时间：
2023-04
影响因子：
1.5
通讯作者：
中科院分区：
文献类型：
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非酒精性脂肪性肝病（NAFLD）是一种常见的慢性肝病，其对药物性肝损伤（DILI）的影响尚不完全清楚。我们研究了NAFLD是否可以影响对乙酰氨基酚（N-乙酰基-对氨基苯酚）诱导的饮食诱导的肥胖（DIO）小鼠模型NAFLD的肝毒性。雄性C57 BL/6 NTac DIO小鼠，喂食高脂肪饮食超过12周，发展为肥胖、高胰岛素血症、葡萄糖耐量受损和肝肿大伴肝脂肪变性，与人类NAFLD相似。在急性毒性研究中，与对照瘦小鼠相比，单剂量APAP（150 mg/kg）后，DIO小鼠血清转氨酶水平降低，肝细胞损伤不太严重。DIO小鼠也改变了与APAP代谢相关的基因表达。与瘦小鼠相比，26周的慢性APAP暴露并没有使患有NAFLD的DIO小鼠更严重的肝毒性。这些结果表明，C57 BL/6 NTac DIO小鼠模型似乎比瘦小鼠对APAP诱导的肝毒性更耐受，这可能与脂肪肝中异生物质代谢能力的改变有关。APAP和其他药物在NAFLD动物模型中的进一步机制研究对于研究某些人类NAFLD患者对内源性DILI的易感性改变的机制是必要的。
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease and its influence on drug-induced liver injury (DILI) is not fully understood. We investigated whether NAFLD can influence acetaminophen (APAP (N-acetyl-p-aminophenol))-induced hepatotoxicity in a diet-induced obese (DIO) mouse model of NAFLD. The male C57BL/6NTac DIO mice, fed a high-fat diet for more than 12 weeks, developed obesity, hyperinsulinemia, impaired glucose tolerance, and hepatomegaly with hepatic steatosis, similar to human NAFLD. In the acute toxicity study after a single dose of APAP (150 mg/kg), compared to control lean mice, the DIO mice had decreased serum transaminase levels and less severe hepatocellular injury. The DIO mice also had altered expression of genes related to APAP metabolism. Chronic APAP exposure for 26 weeks did not predispose the DIO mice with NAFLD to more severe hepatotoxicity compared to the lean mice. These results suggested that the C57BL/6NTac DIO mouse model appears to be more tolerant to APAP-induced hepatotoxicity than lean mice, potentially related to altered xenobiotic metabolizing capacity in the fatty liver. Further mechanistic studies with APAP and other drugs in NAFLD animal models are necessary to investigate the mechanism of altered susceptibility to intrinsic DILI in some human NAFLD patients.
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影响因子：
5.1
作者：
Kleiner DE;Makhlouf HR
通讯作者：
Makhlouf HR
影响因子：
7.3
作者：
Lau, Jennie Ka Ching;Zhang, Xiang;Yu, Jun
通讯作者：
Yu, Jun
影响因子：
1.8
作者：
Cederbaum AI;Yang L;Wang X;Wu D
通讯作者：
Wu D
影响因子：
25.7
作者：
Asrani, Sumeet K.;Devarbhavi, Harshad;Kamath, Patrick S.
通讯作者：
Kamath, Patrick S.
DOI：
10.18053/jctres.03.2017s1.006
发表时间：
2017-03
期刊：
Journal of clinical and translational research
影响因子：
--
作者：
Massart J;Begriche K;Moreau C;Fromenty B
通讯作者：
Fromenty B