Abstract
Paraquat is a toxic herbicide that may induce acute lung injury, circulatory failure and death. The present work aimed at investigating whether there is systemic inflammation and vascular dysfunction after paraquat exposure and whether these parameters were related. There was neutrophilia and accumulation of neutrophils in lung and bronchoalveolar lavage of animals given paraquat. This was associated with an increase in serum levels of TNF-α. In rats given paraquat, the relaxant response of aortic rings to acetylcholine was not modified but the contractile response to phenylephrine was greatly reduced. Endothelium removal or treatment with non-selective (L-NAME) or selective (L-NIL) inhibitors of inducible nitric oxide synthase (iNOS) restored contraction of aortas. There was greater production of nitric oxide (NO), which was restored to basal level by L-NIL, and greater expression of iNOS in endothelial cells, as seen by Western blot analyses and confocal microscopy. Blockade of TNF-α reduced pulmonary and systemic inflammation and vascular dysfunction. Together, our results clearly show that paraquat causes pulmonary and systemic inflammation, and vascular dysfunction in rats. Vascular dysfunction is TNF-α dependent, associated with enhanced expression of iNOS in aortic endothelial cells and greater NO production, which accounts for the decreased responsiveness of aortas to vasoconstrictors. Blockers of TNF-α may be useful in patients with paraquat poisoning.
Highlights
Paraquat (1,1’-dimethyl-4,4’-bipyridinium dichloride) is a nonselective and contact herbicide used worldwide and cause high mortality rate after accidental or deliberate self-poisoning [1]
No mortality was seen after etanercept given before paraquat exposure, or 1h or 6 hs after paraquat exposure
There was no macrophage infiltration in the lung, as assessed by measuring NAG (OD) per 100 mg of tissue: 0.97 ± 0.07 and 0.92 ± 0.07, control and paraquat, respectively, and the total number of leukocytes in bronchoalveolar lavage (BAL) and blood were unaltered (Figure 2A and Figure 2C)
Summary
Paraquat (1,1’-dimethyl-4,4’-bipyridinium dichloride) is a nonselective and contact herbicide used worldwide and cause high mortality rate (more than 50%) after accidental or deliberate self-poisoning [1]. The mechanism underling vascular malfunctioning in paraquat intoxication is largely unknown and most studies have focused on direct in vitro vascular effects of paraquat. In this regard, it is well known that paraquat is capable of producing superoxide, decreasing endothelium-dependent vasorelaxant responses [12,13]. It is well known that paraquat is capable of producing superoxide, decreasing endothelium-dependent vasorelaxant responses [12,13] These data are not in line with the vascular collapse that follows paraquat intoxication and that greatly contributes to early mortality of patients with paraquat poisoning [14,15]. A better understanding of the mechanisms involved in vascular alterations induced by paraquat poisoning may lead to more effective therapies
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
