Signaling pathways involved in paraquat-induced pulmonary toxicity: Molecular mechanisms and potential therapeutic drugs

Paraquat poisoning is a severe health problem globally, particularly in developing countries. Due to its severe toxicity, the mortality rate of paraquat poisoning is greatly higher than other pesticide poisoning. Paraquat accumulates in the lung by specific polyamine uptake and causes a great amount of reactive oxygen species generation induced by redox cycling. Free radicals can further cause cellular damage via lipid peroxidation, mitochondrial damage, inflammatory response, and apoptosis in many organs including lung, liver, and kidney. The potential mechanisms of paraquat toxicity in the lung are extremely complicated. In this review, the biochemical mechanisms and pathophysiological process of paraquat-induced pulmonary toxicity are systematically elaborated based on previous studies. Furthermore, the signaling pathways including Nrf2/ARE, NF-κB, NLRP3 inflammasome, TLRs, PPAR-γ, MAPKs, AMPK, Rho/ROCK, PI3K/Akt/mTOR, TGF-β/Smad, and Wnt/β-catenin and the potential therapeutic drugs are comprehensively summarized. Further studies are still required to evaluate the efficacy of these drugs in the future.