Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review.
Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review.
复制标题
对乙酰氨基酚诱导的肥胖症和非酒精性脂肪肝疾病中的肝毒性：一项关键综述。
DOI：
10.3390/livers3010003
复制
发表时间：
2023-03
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
肥胖、2型糖尿病和非酒精性肝病（NAFLD）的流行有利于药物消费，这增加了包括肝损伤在内的不良事件的风险。30多年来，一系列实验和临床研究报告或建议，常见的止痛药对乙酰氨基酚（APAP）在肥胖和相关代谢疾病中可能更具肝毒性，至少在过量服用后。然而，一些调查没有重现这些数据。这种差异可能来自肥胖和脂肪变性的程度、特定脂质种类的积累、线粒体功能障碍和糖尿病相关参数，如酮血症和高血糖症。在这些因素中，其中一些似乎是关键的诱导细胞色素P450 2 E1（CYP 2 E1），这有利于转化APAP的毒性代谢产物N-乙酰基-对苯醌亚胺（NAPQI）。相比之下，其他因素可能解释了为什么肥胖和NAFLD并不总是与更频繁或更严重的APAP诱导的急性肝毒性相关，例如体内分布容积增加，肝脏葡萄糖醛酸化升高和CYP 3A 4活性降低。因此，在患有NAFLD的肥胖个体中APAP诱导的肝损伤的发生和结果将取决于增加NAPQI生成的代谢因素与可以减轻肝毒性的其他代谢因素之间的微妙平衡。
The epidemic of obesity, type 2 diabetes and nonalcoholic liver disease (NAFLD) favors drug consumption, which augments the risk of adverse events including liver injury. For more than 30 years, a series of experimental and clinical investigations reported or suggested that the common pain reliever acetaminophen (APAP) could be more hepatotoxic in obesity and related metabolic diseases, at least after an overdose. Nonetheless, several investigations did not reproduce these data. This discrepancy might come from the extent of obesity and steatosis, accumulation of specific lipid species, mitochondrial dysfunction and diabetes-related parameters such as ketonemia and hyperglycemia. Among these factors, some of them seem pivotal for the induction of cytochrome P450 2E1 (CYP2E1), which favors the conversion of APAP to the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). In contrast, other factors might explain why obesity and NAFLD are not always associated with more frequent or more severe APAP-induced acute hepatotoxicity, such as increased volume of distribution in the body, higher hepatic glucuronidation and reduced CYP3A4 activity. Accordingly, the occurrence and outcome of APAP-induced liver injury in an obese individual with NAFLD would depend on a delicate balance between metabolic factors that augment the generation of NAPQI and others that can mitigate hepatotoxicity.
登录
查看更多内容
在非酒精性脂肪肝疾病中诱导CYP2E1。
影响因子：
3.6
作者：
Aljomah G;Baker SS;Liu W;Kozielski R;Oluwole J;Lupu B;Baker RD;Zhu L
通讯作者：
Zhu L
影响因子：
2.9
作者：
Abusabeib A;El Ansari W;Alobaidan J;Elhag W
通讯作者：
Elhag W
影响因子：
3.7
作者：
通讯作者：
--
影响因子：
4.3
作者：
Akakpo JY;Ramachandran A;Jaeschke H
通讯作者：
Jaeschke H
影响因子：
3.8
作者：
Al Nebaihi, Hamdah M.;Al Batran, Rami;Brocks, Dion R.
通讯作者：
Brocks, Dion R.