Melatonin ameliorates acute lung injury caused by paraquat poisoning by promoting PINK1 and BNIP3 expression

Abstract

AbstractParaquat (PQ) poisoning can result in multiple organ dysfunction syndrome, mainly manifesting as acute lung injury and acute respiratory distress syndrome. No specific cure exists for PQ poisoning. However, by scavenging mitochondrial DNA (mtDNA), the damage-associated molecular pattern during PQ poisoning, mitophagy can ameliorate the downstream inflammatory pathways activated by mtDNA. Melatonin (MT), however, can promote the expression of PINK1 and BNIP3, which are key proteins involved in mitophagy. In this study, we first explored whether MT could reduce PQ-induced acute lung injury by affecting mitophagy in animal models, and then, we studied the specific mechanism associated with this process through in vitro experiments. We also evaluated MT intervention in the PQ group, while inhibiting the expression of PINK1 and BNIP3, to further determine whether the protective effects of MT are associated with its effect on mitophagy. We found that when the expression of PINK1 and BNIP3 was inhibited, MT intervention could not reduce mtDNA leakage and the release of inflammatory factors caused by PQ exposure, suggesting that the protective effect of MT was mitigated. These results suggest that by promoting the expression of PINK1 and BNIP3 and activating mitophagy, MT can reduce mtDNA/TLR9-mediated acute lung injury during PQ poisoning. The results of this study could provide guidance for the clinical treatment of PQ poisoning to reduce associated mortality.