代谢组学
化学
新陈代谢
生物化学
药理学
代谢组
体内
尿
代谢物
胆汁酸
谷胱甘肽
氧化应激
排泄
药物代谢
牛磺酸
毒性
代谢途径
葡萄糖醛酸
作者
Qiong Zhang,Xuhong Chang,Xiaoxia Wang,Haibing Zhan,Qing Gao,Mengmeng Yang,Han Liu,Sheng Li,Yingbiao Sun
出处
期刊:Toxicology Research
[Oxford University Press]
日期:2021-06-14
卷期号:10 (3): 579-591
标识
DOI:10.1093/toxres/tfab039
摘要
Nickel oxide nanoparticles (Nano NiO) evoke hepatotoxicity, while whether it affects the hepatic metabolism remains unclear. The aim of this study was to explore the differential metabolites and their metabolic pathways in rat serum and to further verify the potential mechanism of bile acids' (BAs) metabolism dysregulation after Nano NiO exposure. Sixteen male Wistar rats were intratracheally instilled with Nano NiO (0.24 mg/kg body weight) twice a week for 9 weeks. Liquid chromatography/mass spectrometry was applied to filter the differentially expressed metabolites in rat serum. Western blot was employed to detect the protein contents. Twenty-one differential metabolites that associated with BAs, lipid and phospholipid metabolism pathways were identified in rat serum after Nano NiO exposure. Decreased cholic acid and deoxycholic acid implied that the BAs metabolism was disturbed. The nickel content increased in liver after Nano NiO exposure. The protein expression of cholesterol 7α-hydroxylase (CYP7A1) was down-regulated, and the bile salt export pump was up-regulated after Nano NiO administration in rat liver. Moreover, dehydroepiandrosterone sulphotransferase (SULT2A1) and cytochrome P450 (CYP) 3A4 were elevated in the exposure group. In conclusion, Nano NiO might trigger the disturbances of BAs, lipid and phospholipid metabolism pathways in rats. The diminished serum BAs induced by Nano NiO might be related to the down-regulation of synthetase and to the overexpression of transmembrane protein and detoxification enzymes in BAs metabolism.
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