Txnrd3 knockout enhancement of lung injury induced by Ni exposure via the VEGF-VEGFR-2 axis and alleviation of this effect by melatonin

Ni exposure leads to respiratory diseases in mice. Txnrd3 has been shown to have a protective effect on the body, but there is a paucity of empirical research focusing specifically on lung tissue. Melatonin possesses potent antioxidant, anti-inflammatory, and anti-fibrotic effects. By regulating inflammation-related factors, melatonin can activate the VEGF signaling pathway, ultimately alleviating lung injuries caused by Ni exposure.One hundred and sixty 8-week-old C57BL/6N mice, that were wild-type or Txnrd3-/- mice and 25-30 g in weight, were randomly divided into eight groups, including the NC group, Ni group, melatonin-treated group, and Ni plus melatonin group. Ni (10 mg/kg) was gavaged, and melatonin (2 mg/kg) was administered for 21 days.Inflammatory cells were found in the bronchioles of Txnrd3-/- mice under Ni exposure. Ultrastructural examination revealed that the homozygous-Ni group had a high amount of collagen fibers. The antioxidant capacity studies also revealed that mice lungs underwent oxidative stress. The results of qRT-PCR and WB showed that Ni induced an inflammatory response, which was also aggravated in Txnrd3-/- mice. Melatonin can effectively reduce the above symptoms. In conclusion, Ni causes lung injury by activating the VEGF-VEGFR-2 pathway and Txnrd3 knockout aggravates injury after Ni exposure.

Automated summary

Exposure to nickel can cause respiratory diseases in mice. Melatonin has been shown to have a protective effect on lung tissue by regulating inflammation-related factors and activating the VEGF signaling pathway.