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A metabolomic-based study on disturbance of bile acids metabolism induced by intratracheal instillation of nickel oxide nanoparticles in rats
- Source :
- Toxicol Res (Camb)
- Publication Year :
- 2021
- Publisher :
- Oxford University Press (OUP), 2021.
-
Abstract
- 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.
- Subjects :
- Paper
0303 health sciences
medicine.medical_specialty
biology
Health, Toxicology and Mutagenesis
Deoxycholic acid
Cholic acid
Phospholipid
Cytochrome P450
Metabolism
Toxicology
Cholesterol 7 alpha-hydroxylase
Bile Salt Export Pump
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
chemistry
030220 oncology & carcinogenesis
Internal medicine
medicine
biology.protein
Drug metabolism
030304 developmental biology
Subjects
Details
- ISSN :
- 20454538
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Toxicology Research
- Accession number :
- edsair.doi.dedup.....36888c6f764a9d7c51e0ea8fe1354fed