Molybdenum and cadmium co‐exposure promotesM1macrophage polarization through oxidative stress‐mediated inflammatory response and induces pulmonary fibrosis inShaoxing ducks (Anas platyrhyncha)

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 H2O2 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.

Triphenyl phosphate‐induced macrophages dysfunction by activation TLR4‐mediated ERK/NF‐κB pathway

“…TPHP has been considered to be related to chronic inflammatory diseases, such as obesity through lipid metabolism disorders, inducing the formation of foam cells, promoting the development of atherosclerosis 30 . Macrophages usually play a key role in these diseases, which means that TPHP may also have toxic effects on immune cells 31,32 . In order to verify underlying immune toxicity of TPHP and its association with immune diseases, RAW 264.7 cells were used in this study, which is one of the important models representing the in vitro evaluation of macrophages.…”

“…30 Macrophages usually play a key role in these diseases, which means that TPHP may also have toxic effects on immune cells. 31,32 In order to verify underlying immune toxicity of TPHP and its association with immune diseases, RAW 264.7 cells were used in this study, which is one of the important models representing the in vitro evaluation of macrophages.…”

Environmentally relevant levels of Cd and Mo coexposure induces ferroptosis and excess ferritinophagy through AMPK/mTOR axis in duck myocardium

“…increase malondialdehyde (MDA) content, and then aggravate occurrence of lipid peroxidation (LPO) in the body, ultimately causing damage to organisms. 10 Hence, the biological toxicity of excess Mo has been widely concerned by many researchers. Environmental Mo and Cd levels are rapidly increasing due to industrial production and human activities.…”

“…The kidney, testicle, ovary, and heart are the primary organs damaged by Mo toxicity 8,9 . Study has shown that high concentrations of Mo can significantly reduce glutathione peroxidase (GSH‐px) and glutathione (GSH) activities and increase malondialdehyde (MDA) content, and then aggravate occurrence of lipid peroxidation (LPO) in the body, ultimately causing damage to organisms 10 . Hence, the biological toxicity of excess Mo has been widely concerned by many researchers.…”