Intranasal curcumin mitigates paraquat-induced oxidative lung damage via involvement of neutrophil extracellular traps (NETs) in mice model.

Abstract

Paraquat (PQ) is a highly toxic herbicide that causes rapid and severe lung injury via oxidative stress and inflammatory activation. The present study aimed to investigate the protective effects of curcumin on PQ inhalation-induced lung injury in a mice model. Therefore, the intranasal route of PQ administration was selected, where mice were euthanized after 48 h of PQ exposure. Enhanced oxidative damage and the formation of neutrophil extracellular traps were released by activated neutrophils, along with elevated inflammatory mediators. Oxidative stress-induced lung injury was accompanied with increased DNA damage and reduced antioxidant defenses. Lung injury severity was higher with intranasal PQ in terms of inflammatory cell infiltration and early fibrotic changes, with collagen deposition around the bronchioles. Reduced E-cadherin, a marker of epithelial cells, and enhanced α-SMA were noted, showing enhanced epithelial to mesenchymal transition (EMT) in PQ-induced groups, which was reduced in intranasal curcumin treatment groups. Substantially reduced oxidative stress, NF-kB expression, and enhanced Nrf2 levels were noted, indicative of restored antioxidant enzymes and limited inflammatory responses, signifying a protective effect against PQ-induced lung injury. Immunofluorescence and protein expression analysis revealed fibrotic changes in the lungs, where enhanced alpha smooth muscle actin (α-SMA) and MMP9 expressions were reduced with intranasal curcumin treatment.