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Arsenic Trioxide Triggers Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis via Nrf 2/Caspase 3 Signaling Pathway in Heart of Ducks

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Abstract

Arsenic is a common environmental pollutant and poses a serious threat to human and animal health. In this study, we used the ducks to mimic arsenic trioxide (ATO) exposure and investigated the mechanism of cardiac toxicity. The results indicated that ATO inhibited the body and organ growth of ducks, led to an increase in LDH content, and caused obvious deformity, ischemia infarction. It is found that ATO exacerbated the swell of mitochondrial and the contraction of cell nuclei in the heart of ducks through transmission electron microscopy (TEM). ATO also induced an increase in MDA content; inhibited the activation of the Nrf 2 pathway; downregulated the expression of mRNA and protein of Nrf 2, HO-1, and SOD-1; and upregulated the expression of mRNA and protein of Keap 1. At the same time, ATO induced apoptosis which not only upregulated the expression levels of mRNA and proteins (Caspase 3, Cyt-C, P53, Bax) but also decreased the mRNA and protein expression level of Bcl-2. These results indicated that ATO can lead to oxidative stress and apoptosis in the heart of ducks. In general, our research shows that ATO triggers mitochondrial dysfunction, oxidative stress, and apoptosis via Nrf 2/Caspase 3 signaling pathway in the heart of ducks.

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Funding

This work was supported by the National Natural Science Foundation of China (#31402264), the Guangzhou Science and Technology Program key projects (#201803020003), and Program of Department of Natural Resources of Guangdong Province (Nos. GDME2018C014 and GDNRC [2020]038).

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Authors and Affiliations

  1. College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China

    Gan Rao, Gaolong Zhong, Ting Hu, Shaofeng Wu, Jiajia Tan, Zhaoxin Tang & Lianmei Hu

  2. Joint Laboratory of Guangdong Province and Hong Kong Region On Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China

    Xiaoyong Zhang

  3. Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou, 510642, China

    Riming Huang

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  1. Gan Rao
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  2. Gaolong Zhong
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  3. Ting Hu
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  4. Shaofeng Wu
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Contributions

Conceptualization: Gan Rao; methodology: Gan Rao, Gaolong Zhong, Shaofeng Wu; formal analysis and investigation: Gan Rao, Gaolong Zhong; writing-original draft preparation: Gan Rao; writing — review and editing: Jiajia Tan, Lianmei Hu; funding acquisition: Lianmei Hu; resources: Lianmei Hu; supervision: Xiaoyong Zhang, Riming Huang, Zhaoxin Tang, Lianmei Hu.

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Correspondence to Lianmei Hu.

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The original version of this article was revised to correct Figures 5 and 6.

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Rao, G., Zhong, G., Hu, T. et al. Arsenic Trioxide Triggers Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis via Nrf 2/Caspase 3 Signaling Pathway in Heart of Ducks. Biol Trace Elem Res 201, 1407–1417 (2023). https://doi.org/10.1007/s12011-022-03219-1

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