Novel insights into cytochrome P450 enzyme and solute carrier families in cadmium-induced liver injury of pigs

• Published in: Ecotoxicology and environmental safety Vol. 211; p. 111910
• Main Authors: Wang, Huan, Han, Qi, Chen, Yongjie, Hu, Guanghui, Xing, Houjuan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.03.2021; Elsevier
• Subjects: Animals; Antioxidants - pharmacology; Cadmium; Cadmium - toxicity; Chemical and Drug Induced Liver Injury, Chronic - enzymology; Chemical and Drug Induced Liver Injury, Chronic - pathology; Cytochrome P-450 Enzyme System - metabolism; Cytochrome P450 enzyme family; Environmental Pollutants - toxicity; Liver - drug effects; Organic Anion Transporters, Sodium-Independent - genetics; Organic Anion Transporters, Sodium-Independent - pharmacology; Pig; RNA, Messenger - genetics; Solute carrier family; Swine; Transcriptome - drug effects; Transcriptomics; Solute carrier family; Cytochrome P450 enzyme family; Cadmium; Transcriptomics; Pig
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2021.111910

Cadmium (Cd) is a typical pollutant and carcinogen in environment. Exposure assessment of contaminants is an important component of occupational and environmental epidemiological studies. Early studies of Cd have focused on aquatic animals, chickens and rats. However, toxicological evaluation of Cd in pigs has not been reported. Therefore, twelve pigs were randomly divided into two groups (n = 6): the control group and the Cd group (Cd content: 15 ± 0.242 mg/kg feed) in this study, the experimental period was 30 d, and the toxic effects of Cd on the liver of weanling piglets were examined by antioxidant function, liver function, Cd content, histological examination and transcriptomics. The results showed that the changes of antioxidant function, liver function and Cd content were significant in the liver. Transcriptional profiling results showed that 399 differentially expressed genes (DEGs) were significantly up-regulated while 369 DEGs were remarkably down-regulated in Cd group, and which were concentrated in three ontologies: molecular function, cellular component and biological processes. Interestingly, significant changes in some genes of the cytochrome P450 enzyme (CYP450) and solute carrier (SLC) families have been observed and were consistent with qRT-PCR results. In conclusion, Cd could cause liver injury in weanling piglets and change the transcriptomic characteristics of liver. CYP450 and SLC families play an indispensable role in Cd-mediated hepatotoxicity. Importantly, changes in mRNA levels of CYP2B22, CYP7A1, CYP8B1, SLC26A8, SLC11A1, SLC27A2 and SLC22A7 induced by Cd have been reported for the first time. Our findings will provide a new insight for better assessing the mechanism of Cd toxicity to the liver. [Display omitted] •Cadmium (Cd) exposure can cause liver damage in weaned piglets.•Cd exposure changed transcriptomic characteristics of liver in weanling piglets.•CYP450 and SLC families play an indispensable role in Cd-mediated hepatotoxicity.•Cd can cause the changes of CYP2B22, CYP7A1, and CYP8B1.•Our study proves for the first time that Cd causes the changes in SLC family genes.