Abstract
Arsenic trioxide (ATO), a trivalent arsenic compound, is known to disrupt redox homeostasis. Methionine sulfoxide reductases (Msrs), a group of antioxidant proteins, convert methionine sulfoxide back to methionine in living organisms exposed to oxidative stress. The objective of this study was to determine the effects of ATO on oxidative stress and the expressions of Msrs in mouse liver. Sixty male mice were randomly divided into six equal groups: one control group and five groups that received ATO treatment (0.3, 1, 3, 6, and 9 mg/kg, respectively). After a 4-week treatment, livers specimens were collected and assayed for malonyldialdehyde (MDA) content, superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) activity. In addition, the mRNA expressions of SOD-1 and HO-1 and the mRNA and protein expressions of Msrs were also determined. Results showed that the T-AOC activity, SOD activity, and SOD-1 mRNA expression were significantly decreased (P < 0.01), while the GSH-Px level, MDA content, and HO-1 mRNA expression were significantly increased in mice treated with ATO compared with control. Levels of MsrB2 mRNA and MsrA protein were significantly increased by ATO treatment, except in the highest dose group. There were no significant changes in MsrB3 mRNA level. ATO, at 1 or 3 mg/kg, increased MsrB1 expression. Modifications in MsrA protein level were consistent with changes in mRNA levels. Collectively, our results suggest that ATO induced oxidative stress and then led to the variations in Msrs activity in mouse liver.
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Acknowledgments
All authors thank Shuai Zhang, Xinyan Ma, Feiyang Ma, and Yuyin Lin for their help in the animal experiments in the clinical veterinary medicine laboratory at the College of Veterinary Medicine, South China Agricultural University.
Funding
This work was supported by the National Natural Science Foundation of China (31402264, 31572585), Guangzhou Planned Program in Science and Technology (No. 201803020003), and the National Key R&D Program of China (grant numbers 2016YFD0501205, 2017YFD0502200).
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All animal procedures were approved by the Institutional Animal Care and Use Committee of the South China Agricultural University.
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Zhong, G., Wan, F., Yan, H. et al. Methionine Sulfoxide Reductases Are Related to Arsenic Trioxide-Induced Oxidative Stress in Mouse Liver. Biol Trace Elem Res 195, 535–543 (2020). https://doi.org/10.1007/s12011-019-01881-6
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DOI: https://doi.org/10.1007/s12011-019-01881-6