Paraquat (PQ), a highly toxic herbicide and primary attack for lung, results in severe acute lung injury (ALI) appeared as evident oxidative stress, inflammation, and apoptosis. Increasing evidence elucidates that nuclear factor erythroid-2-related factor 2 (Nrf2) and its associated nuclear factor-κB (NF-κB) exhibit many merits for protection of ALI by coordinating a fine-turned response to oxidative stress, inflammation, and apoptosis. Ginkgolide C (GC) has been reported to be a safe and potent therapeutic agent against ALI. However, whether GC could protect ALI induced by PQ poisoning and the possible underlining mechanisms have remained not to be fully elucidated. A rat model of ALI and a model of acute type II alveolar epithelial cell (RLE-6TN) injury constructed by exposure to PQ were applied to discuss the protective effect of GC. Furthermore, Nrf2 gene silencing RLE-6TN cells were used to discuss the exact mechanism. We confirmed that GC significantly ameliorated the histopathological damages, ultrastructural changes, lung injury score, W/D ratio, and Hyp activity of lung tissue and inhibited polymorphonuclear neutrophil (PMN) infiltration after PQ poisoning. Further results revealed that GC remarkably activated Nrf2-based cytoprotective system and inhibited NF-κB-induced inflammatory injury as well as apoptosis. Taken together, we concluded that GC preserved protection of PQ-induced ALI via the Nrf2-NF-κB dependent signal pathway, which may provide us novel insights into the treatment strategies for PQ poisoning.
Copyright © 2022 Rui Zhang et al.