title: An effective antidote for paraquat poisonings: the treatment with lysine acetylsalicylate.
abstract: Sodium salicylate (NaSAL) has been shown to have a multifactorial protection mechanism against paraquat (PQ)-induced toxicity, due to its ability to modulate inflammatory signalling systems, to prevent oxidative stress and to its capacity to chelate PQ. Considering that currently there is no pharmaceutical formulation available for parenteral administration of NaSAL, the aim of the present study was to evaluate the antidotal feasibility of a salicylate prodrug, lysine acetylsalicylate (LAS), accessible for parenteral administrations. PQ was administered to Wistar rats by gavage (125mg/kg of PQ ion) and the treatment was performed intraperitoneally with different doses (100, 200 and 400mg/kg of body weight) of LAS. Survival rate was followed during 30 days and living animals at this endpoint were sacrificed for lung, kidney, liver, jejune and heart histological analysis. It was shown, that the salicylate prodrug, LAS, available in a large number of hospitals, is also effective in the treatment of PQ intoxications. From all tested LAS doses, 200mg/kg assured animal's full survival. Comparatively to 60% of mortality observed in PQ only exposed animals, the lethality was higher (80%) in the group that received 400mg/kg of LAS 2h after PQ administration. The dose of 100mg/kg of LAS showed only a modest protection (60% of survival). Collagen deposition was observed by histological analysis in survived animals of all experimental groups, being less pronounced in animals receiving 200mg/kg of LAS, reinforcing the importance of this dose against tissue damage induced by PQ. The results allow us to suggest that LAS should be considered in the hospital treatment of PQ poisonings.
authors.affiliation: REQUIMTE, Department of Toxicology, Faculty of Pharmacy, University of Porto, Porto, Portugal. ricardinis@sapo.pt
authors.forename: R J
authors.initials: RJ
authors.lastname: Dinis-Oliveira
authors.forename: H
authors.initials: H
authors.lastname: Pontes
authors.forename: M L
authors.initials: ML
authors.lastname: Bastos
authors.forename: F
authors.initials: F
authors.lastname: Remião
authors.forename: J A
authors.initials: JA
authors.lastname: Duarte
authors.forename: F
authors.initials: F
authors.lastname: Carvalho
mesh_terms: D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D001241:Aspirin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007583:Jejunum / Q000473:pathology; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008239:Lysine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D009206:Myocardium / Q000473:pathology; D010269:Paraquat / Q000506:poisoning*; D011041:Poisoning / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000931:Antidotes; D008239:Lysine; D010269:Paraquat; D001241:Aspirin; C010395:acetylsalicylic acid lysinate