Molybdenum and cadmium co‐exposure promotes M1 macrophage polarization through oxidative stress‐mediated inflammatory response and induces pulmonary fibrosis in S haoxing ducks ( Anas platyrhyncha )

• Published in: Environmental toxicology Vol. 37; no. 12; pp. 2844 - 2854
• Main Authors: Huang, Gang, Luo, Junrong, Guo, Huiling, Wang, Xueru, Hu, Zhisheng, Pu, Wenjing, Chu, Xuesheng, Zhang, Caiying
• Format: Journal Article
• Language: English
• Published: 01.12.2022
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.23641

Abstract High molybdenum (Mo) and cadmium (Cd) are harmful to the body, but pulmonary toxicity induced by Mo and Cd co‐exposure is unknown. To assess the combined impacts of Mo and Cd on fibrosis through M1 polarization in the lung of ducks, 80 healthy 8‐day‐old Shaoxing ducks ( Anas platyrhyncha ) were randomly assigned to 4 groups and fed with containing unequal doses of Mo or/and Cd diet. Lung tissues were collected on the 16th week. Results indicated that Mo or/and Cd significantly increased their contents in the lungs, and led to trace elements disorder and histological abnormality, and oxidative stress accompanied by promoting contents of H 2 O 2 and MDA and decreasing activities of T‐SOD, GSH‐Px, and CAT, then activated the TLR4/NF‐κB/NLRP3 pathway accompanied by upregulating Caspase‐1, ASC, IL‐18, IL‐1β, TLR4, NF‐κB, and NLRP3 expression levels, and disrupted M1/M2 balance to divert toward M1, which evoked the TGF‐β/Smad2/3‐mediated fibrosis by elevating TGF‐β1, Smad2, Smad3, COL1A1, α‐SMA, and MMP2 expression levels, and decreasing Smad7 and TIMP2 expression levels. The changes of the combined group were most obvious. To sum up, the research demonstrated that Mo or/and Cd may cause macrophages to polarize toward M1 by oxidative stress‐mediated the TLR4/NF‐κB/NLRP3 pathway, then result in fibrosis through the TGF‐β1/Smad2/3 pathway in duck lungs. Mo and Cd may worsen lung damage.