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Different Sources of Copper Effect on Intestinal Epithelial Cell: Toxicity, Oxidative Stress, and Metabolism

by Runxian Li 1,†, Yang Wen 1,†, Gang Lin 2, Chengzhen Meng 1, Pingli He 1,* and Fenglai Wang 1,*
1
State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
2
Institute of Quality Standards and Testing Technology for Agricultural Products, Chinese Academy of Agricultural Science, Key Laboratory of Agrifood Safety and Quality, Ministry of Agriculture, Beijing 100081, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Metabolites 2020, 10(1), 11; https://doi.org/10.3390/metabo10010011
Received: 3 December 2019 / Revised: 19 December 2019 / Accepted: 20 December 2019 / Published: 23 December 2019
Copper (Cu) is widely used in the swine industry to improve the growth performance of pigs. However, high doses of copper will induce cell damage and toxicity. The aim of this study was to evaluate toxicity, bioavailability, and effects on metabolic processes of varying copper sources using porcine intestinal epithelial cells (IPEC-J2) as a model. The IPEC-J2 were treated with two doses (30 and 120 μM) of CuSO4, Cu Glycine (Cu-Gly), and Cu proteinate (Cu-Pro) for 10 h, respectively. Cell damage and cellular copper metabolism were measured by the changes in cell viability, copper uptake, oxidative stress biomarkers, and gene/protein expression levels. The results showed that cell viability and ratio of reduced and oxidized glutathione (GSH/GSSG) decreased significantly in all treatment groups; intracellular copper content increased significantly in all treatment groups; total superoxide dismutase (SOD) activity increased significantly in the 120 μM exposed groups; SOD1 protein expression levels were significantly upregulated in 30 μM Cu-Pro, 120 μM Cu-Gly, and 120 μM Cu-Pro treatment groups; intracellular reactive oxygen species (ROS) generation and malondialdehyde (MDA) content increased significantly in 30 μM treatment groups and 120 μM CuSO4 treatment group. CTR1 and ATP7A gene expression were significantly downregulated in the 120 μM exposed groups. While upregulation of ATOX1 expression was observed in the presence of 120 μM Cu-Gly and Cu-Pro. ASCT2 gene expression was significantly upregulated after 120 μM Cu-Glycine and CuSO4 exposure, and PepT1 gene expression was significantly upregulated after Cu-Pro exposure. In addition, CTR1 protein expression level decreased after 120 μM CuSO4 and Cu-Gly exposure. PepT1 protein expression level was only upregulated after 120 μM Cu-Pro exposure. These findings indicated that extra copper supplementation can induce intestinal epithelial cell injury, and different forms of copper may have differing effects on cell metabolism. View Full-Text
Keywords: copper; cytotoxicity; bioavailability; oxidative stress; intestinal epithelial cell copper; cytotoxicity; bioavailability; oxidative stress; intestinal epithelial cell
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Li, R.; Wen, Y.; Lin, G.; Meng, C.; He, P.; Wang, F. Different Sources of Copper Effect on Intestinal Epithelial Cell: Toxicity, Oxidative Stress, and Metabolism. Metabolites 2020, 10, 11.

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