Abstract
Paraquat (PQ) has been one of the most widely used herbicides in the world. PQ, when ingested, is toxic to humans and may cause acute respiratory distress syndrome. To investigate molecular perturbation in lung tissues caused by PQ, Sprague Dawley male rats were fed with PQ at a dose of 25 mg/kg body weight for 20 times in four weeks. The effects of PQ on cellular processes and biological pathways were investigated by analyzing proteome in the lung tissues in comparison with the control. Among the detected proteins, 321 and 254 proteins were over-represented and under-represented, respectively, in the PQ-exposed rat lung tissues in comparison with the no PQ control. All over- and under-represented proteins were subjected to Ingenuity Pathway Analysis to create 25 biological networks and 38 pathways of interacting protein clusters. Over-represented proteins were involved in the C-jun-amino-terminal kinase pathway, caveolae-mediated endocytosis signaling, cardiovascular-cancer-respiratory pathway, regulation of clathrin-mediated endocytosis, non-small cell lung cancer signaling, pulmonary hypertension, glutamate receptor, immune response and angiogenesis. Under-represented proteins occurred in the p53 signaling pathway, mitogen-activated protein kinase signaling pathway, cartilage development and angiogenesis inhibition in the PQ-treated lungs. The results suggest that PQ may generate reactive oxygen species, impair the MAPK/p53 signaling pathway, activate angiogenesis and depress apoptosis in the lungs.
Highlights
Paraquat (1,1-dimethyl-4,4 ́-bispyridinium dichloride) has been one of the most widely used herbicides in the world since its introduction to the market in 1962 [1]
We have found that tumor suppressor p53-binding protein 1, B-cell lymphoma/leukemia 11B, diphthamide biosynthesis protein 1, hypermethylated in cancer 1 protein, and chromosome transmission fidelity protein 8 homolog isoform 2 were down-represented in the PQ treated groups compared with the control group
The results indicated that p53 signaling pathway was downregulated through activation of Wnt signaling pathway where proteins were over-represented, which included adenomatous polyposis coli protein 2 (APC2), tuber in/tuberous sclerosis 2 (TSC2), leucine-rich repeat flightless-interacting protein 2 (LRRFIP2), dapper homolog 1 (DACT1), GSK-3-binding protein (FRAT2) and microtubule-actin cross-linking factor 1 (MACF1) in the PQ-treated rat lungs
Summary
Paraquat (1,1-dimethyl-4,4 ́-bispyridinium dichloride) has been one of the most widely used herbicides in the world since its introduction to the market in 1962 [1]. It is very toxic to mammals including humans and ingestion may cause acute respiratory distress syndrome. Paraquat accumulates in the human lungs at a concentration 10 times greater than that in the other tissues [2]. The major toxicity is known to cause damages in the tissues of lungs, livers and kidneys. It makes lungs harden and causes severe lung injuries, such as interstitial edema, leukocyte infiltration, alveolar hemorrhage edema, fibroblast proliferation and collagen deposition when it is accumulated in lungs [10,11,12]. The initial phase ends in death of pulmonary edema, cell infiltration and alveolar hemorrhage within a few days. Infiltration and proliferation of fibroblasts may cause fibrosis that eradicates alveolar tissue. No successful treatment has passed clinical trials many treatment protocols for PQ poisoning have been studied [15,16,17,18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
