Molybdenum and Cadmium Co-induce Pyroptosis via Inhibiting Nrf2-Mediated Antioxidant Defense Response in the Brain of Ducks.
Zhisheng HuGaohui NieJunrong LuoRuiming HuGuyue LiGuoliang HuCaiying ZhangPublished in: Biological trace element research (2022)
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.
Keyphrases
- oxidative stress
- nk cells
- computed tomography
- nuclear factor
- binding protein
- hydrogen peroxide
- magnetic resonance imaging
- physical activity
- induced apoptosis
- endoplasmic reticulum stress
- nitric oxide
- protein protein
- toll like receptor
- inflammatory response
- white matter
- multiple sclerosis
- cell proliferation
- immune response
- breast cancer cells
- weight loss
- small molecule
- living cells
- drug induced
- cell cycle arrest
- subarachnoid hemorrhage
- gestational age