RESUMO
The exact toxicological mechanisms of paraquat (PQ) poisoning are not entirely clear, especially on the high-level acute exposure. To assess the health risk of PQ, especially to suicidal individuals, accidental ingestion eaters, occupational groups, and special multitude, firstly we explored the acute toxic effect and the possible mechanisms of high-level exposure of PQ using zebrafish. The mainly target organs of PQ were swim bladder which is the homolog of the mammalian lung, followed by gastrointestinal tract and liver. Morphological malformations which were further defined by histopathologic examination include smaller size, fibrosis and inflammatory cell invasion for swim bladder; irregularly arranged or dissolved epithelial folds, loss of villous architecture, and ecclasis of mucosal cells in a smaller lumen for gastrointestinal tract; as well as smaller size, degeneration, fibrous proliferation, atrophy for liver. In addition, PQ enhanced leukocyte recruitment (neutrophil migrated first, followed by macrophage) into swim bladder and induced ROS which can be scavenged by glutathione. Moreover, qRT-PCR results showed that PQ increased the expression level of genes involved in the inflammatory response, such as L-1ß, IL-6, IL-8, TNF-α, TNF-ß, IFN-1, TGF-ß, and NF-kB. For the first time, our results demonstrated that acute exposure of PQ induced pulmonary toxicity which was followed by gastrointestinal and hepatic toxicity via neutrophil-mediated ROS in zebrafish. In summary, these findings generated here will contribute to our better understanding of characteristics of PQ acute poisoning and can provide valuable information on better PQ poisoning treatments, occupational disease prevention, and providing theoretical foundation for risk management measures.
