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

ABSTRACT: 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 ?M) 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 ?M exposed groups; SOD1 protein expression levels were significantly upregulated in 30 ?M Cu-Pro, 120 ?M Cu-Gly, and 120 ?M Cu-Pro treatment groups; intracellular reactive oxygen species (ROS) generation and malondialdehyde (MDA) content increased significantly in 30 ?M treatment groups and 120 ?M CuSO4 treatment group. CTR1 and ATP7A gene expression were significantly downregulated in the 120 ?M exposed groups. While upregulation of ATOX1 expression was observed in the presence of 120 ?M Cu-Gly and Cu-Pro. ASCT2 gene expression was significantly upregulated after 120 ?M 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 ?M CuSO4 and Cu-Gly exposure. PepT1 protein expression level was only upregulated after 120 ?M 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.

SUBMITTER: Li R

PROVIDER: S-EPMC7022486 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Li Runxian R Wen Yang Y Lin Gang G Meng Chengzhen C He Pingli P Wang Fenglai F

Metabolites 20191223 1

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 CuSO<sub>4</sub>, Cu Glycine (Cu-Gly), and Cu proteinate (Cu-Pro) for 10 h, respectively. C ...[more]

PMID: 31877957

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Project description:Copper (Cu) is an essential trace element in the production of swine. This study was conducted to investigate the effect of 3 different sources of Cu on growth performance, Cu metabolism, and intestinal microorganisms of finishing pigs, so as to estimate the bioavailability of the 3 sources for pigs. A total of 42 male finishing pigs (88.74 ± 5.74 kg) were randomly allocated to 7 treatments. The factors were 3 sources (CuSO4, Cu-glycine, Cu-proteinate) and 2 levels (5 and 20 mg/kg) of Cu, plus one negative control treatment (0 mg/kg added Cu level) for the entire 28-d experiment. The average daily gain (ADG) and feed to gain ratio (F:G) both increased when Cu was added. The Cu level in liver, bile, kidney, serum, lung, urine and feces rose (P < 0.001) with increasing dietary Cu level regardless of the source. Meanwhile, pigs receiving organic Cu (glycinate or proteinate) retained more Cu and excreted less Cu than those receiving inorganic Cu (CuSO4), which showed that organic forms were more bioavailable. At the transcriptional level, changes in the level and source of dietary Cu resulted in modulation of transporters. In the jejunal mucosa, import transporter high affinity copper uptake protein 1 (CTR1) and export transporter ATPase copper transporting alpha (ATP7A) in supplemental Cu treatments were down-regulated compared to the control. Also, peptide transporter 1 (PepT1) and lanine-serine-cysteine transporter, type-2 (ASCT2) were significantly (P < 0.01) up-regulated in 20 mg/kg Cu-proteinate and Cu-glycinate treatments, respectively. Microbial diversity was lowest in the 20 mg/kg CuSO4 treatment, and the ratio of Firmicutes to Bacteroidetes was higher in added Cu treatments, especially Cu-glycinate treatment. These results indicate that uptake of different Cu forms is facilitated by different transporters and transport mechanisms, and compared with inorganic Cu, organic Cu provides benefits to intestinal microflora and reduces Cu excretion.

Dataset Information

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

Publications

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

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