Benzbromarone aggravates hepatic steatosis in obese individuals
文献类型：期刊论文
| 作者 | Sun, Peng1,2; Zhu, Jing-Jie1; Wang, Ting1; Huang, Qi1; Zhou, Yu-Ren1; Yu, Bang-Wei1; Jiang, Hua-Liang1 ; Wang, He-Yao1
|
| 刊名 | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
 |
| 出版日期 | 2018-06 |
| 卷号 | 1864期号:6页码:2067-2077 |
| 关键词 | Benzbromarone Hepatotoxicity Hepatic steatosis Obesity |
| ISSN号 | 0925-4439 |
| DOI | 10.1016/j.bbadis.2018.03.009 |
| 文献子类 | Article |
| 英文摘要 | As a widely used anti-gout drug, benzbromarone has been found to induce hepatic toxicity in patients during clinical treatment. Previous studies have reported that benzbromarone is metabolized via cytochrome P450, thus causing mitochondrial toxicity in hepatocytes. In this study, we found that benzbromarone significantly aggravated hepatic steatosis in both obese db/db mice and high fat diet (HFD)-induced obese (DIO) mouse models. However, benzbromarone had less effect on the liver of lean mice. It was found that the expression of mRNAs encoding lipid metabolism and some liver-specific genes were obviously disturbed in benzbromarone-treated DIO mice compared to the control group. The inflammatory and oxidative stress factors were also activated in the liver of benzbromarone-treated DIO mice. In accordance with the in vivo results, an in vitro experiment using human hepatoma HepG2 cells also confirmed that benzbromarone promoted intracellular lipid accumulation under high free fatty acids (FFAs) conditions by regulating the expression of lipid metabolism genes. Importantly, prolonged treatment of benzbromarone significantly increased cell apoptosis in HepG2 cells in the presence of high FFAs. In addition, in benzbromarone-treated hyperuricemic patients, serum transaminase levels were positively correlated with patients' obesity level. Conclusion: This study demonstrated that benzbromarone aggravated hepatic steatosis in obese individuals, which could subsequently contribute to hepatic cell injury, suggesting a novel toxicological mechanism in benzbromarone-induced hepatotoxicity. |
| WOS关键词 | ENDOPLASMIC-RETICULUM STRESS ; FATTY LIVER-DISEASE ; TRIGLYCERIDE SYNTHESIS ; LIPID-PEROXIDATION ; OXIDATIVE STRESS ; RAT HEPATOCYTES ; ADIPOSE-TISSUE ; UP-REGULATION ; URIC-ACID ; IN-VITRO |
| 资助项目 | National Natural Science Foundation of China[81473262] ; National Natural Science Foundation of China[81773791] ; National Natural Science Foundation of China[81503124] ; National Natural Science Foundation of China[81603169] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120162025] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120164014] ; Natural Science Foundation of Jiangsu Province[BK20161027] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000432105600007 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279739]  |
| 专题 | 药理学第三研究室 上海中药现代化研究中心 |
| 通讯作者 | Wang, He-Yao |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 2.Nanjing Med Univ, Dept Biochem & Mol Biol, Key Lab Human Funct Genom Jiangsu Prov, 140 Hanzhong Rd, Nanjing 210029, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sun, Peng,Zhu, Jing-Jie,Wang, Ting,et al. Benzbromarone aggravates hepatic steatosis in obese individuals[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,2018,1864(6):2067-2077. |
| APA | Sun, Peng.,Zhu, Jing-Jie.,Wang, Ting.,Huang, Qi.,Zhou, Yu-Ren.,...&Wang, He-Yao.(2018).Benzbromarone aggravates hepatic steatosis in obese individuals.BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,1864(6),2067-2077. |
| MLA | Sun, Peng,et al."Benzbromarone aggravates hepatic steatosis in obese individuals".BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 1864.6(2018):2067-2077. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。