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Molybdenum and Cadmium Co-induce Pyroptosis via Inhibiting Nrf2-Mediated Antioxidant Defense Response in the Brain of Ducks

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Abstract

Excess molybdenum (Mo) and cadmium (Cd) are harmful to animals, but the neurotoxic mechanism co-induced by Mo and Cd is unclear. To estimate the effects of Mo and Cd co-exposure on pyroptosis by nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant defense response in duck brains, 40 healthy 7-day-old ducks were randomly assigned to 4 groups and fed diet supplemented with Mo or/and Cd for 16 weeks, respectively. Results showed that Mo or/and Cd markedly increased Mo and Cd contents; decreased iron (Fe), copper (Cu), zinc (Zn), and selenium (Se) contents, elevated malondialdehyde (MDA) content; and decreased total-antioxidant capacity (T-AOC), total-superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities accompanied by pathological damage in brain. Additionally, Mo or/and Cd inhibited Nrf2 pathway via decreasing Nrf2, CAT, SOD1, glutathione S-transferase (GST), hemeoxygenase-1 (HO-1), NAD (P) H:quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC), and modifier subunit (GCLM) mRNA levels and Nrf2 protein level, which induced pyroptosis through upregulating nucleotide oligomerization domain-like receptor protein-3 (NLRP3), apoptosis-associated speck-like protein (ASC), gasdermin A (GSDMA), gasdermin E (GSDME), interleukin-1β (IL-1β), interleukin-18 (IL-18), Caspase-1, NIMA-related kinase 7 (NEK7) mRNA levels and NLRP3, Caspase-1 p20, gasdermin D (GSDMD), ASC protein levels and IL-1β, and IL-18 contents. Besides, the changes of these indicators were most apparent in the Mo and Cd co-treated group. Collectively, the results certificated that Mo and Cd might synergistically induce pyroptosis via inhibiting Nrf2-mediated antioxidant defense response in duck brains, whose mechanism is closely related to Mo and Cd accumulation.

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Funding

The work was supported by the National Natural Science Foundation of China (No. 31960722).

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Authors and Affiliations

  1. Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang, 330045, Jiangxi, China

    Zhisheng Hu, Junrong Luo, Ruiming Hu, Guyue Li, Guoliang Hu & Caiying Zhang

  2. School of Information Technology, Jiangxi University of Finance and Economics, No. 665 Yuping West street, Economic and Technological Development District, Nanchang, 330032, Jiangxi, China

    Gaohui Nie

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  1. Zhisheng Hu
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Zhisheng Hu: conceptualization, software, formal analysis, writing-original draft, data curation, visualization, writing-review and editing, validation. Gaohui Nie: methodology, visualization, resources. Junrong Luo: data curation, validation, formal analysis. Ruiming Hu: data curation, validation, formal analysis. Chenghong Xing: methodology, formal analysis. Guoliang Hu: resources, validation. Caiying Zhang: conceptualization, project administration, writing-review and editing, funding acquisition.

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Hu, Z., Nie, G., Luo, J. et al. Molybdenum and Cadmium Co-induce Pyroptosis via Inhibiting Nrf2-Mediated Antioxidant Defense Response in the Brain of Ducks. Biol Trace Elem Res 201, 874–887 (2023). https://doi.org/10.1007/s12011-022-03170-1

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