Full survival of paraquat-exposed rats after treatment with sodium salicylate.
Over the past decades, there have been numerous fatalities resulting from accidental or voluntary ingestion of the widely used herbicide paraquat dichloride (methyl viologen; PQ). Considering that the main target organ for PQ toxicity is the lung and involves the production of reactive oxygen and nitrogen species, inflammation, disseminated intravascular coagulation, and activation of transcriptional regulatory mechanisms, it may be hypothesized that an antidote against PQ poisonings should counteract all these effects. For this purpose, sodium salicylate (NaSAL) may constitute an adequate therapeutic drug, due to its ability to modulate inflammatory signaling systems and to prevent oxidative stress. To test this hypothesis, NaSAL (200 mg/kg ip) was injected in rats 2 h after exposure to a toxic dose of PQ (25 mg/kg, ip). NaSAL treatment caused a significant reduction in PQ-induced oxidative stress, platelet activation, and nuclear factor (NF)-kappaB activation in lung. In addition, histopathological lesions induced by PQ in lung were strongly attenuated and the oxidant-induced increases of glutathione peroxidase and catalase expression became absent. These effects were associated with a full survival of the PQ-treated rats (extended for more than 30 days) in comparison with 100% of mortality by Day 6 in animals exposed only to PQ, suggesting that NaSAL constitutes an important and valuable therapeutic drug to be used against PQ-induced toxicity. Indeed, NaSAL constitutes the first compound with such degree of success (100% survival).
Dinis-Oliveira
R J
RJ
REQUIMTE, Departamento de Toxicologia, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4099-030 Porto, Portugal. ricardinis@ff.up.pt
Sousa
C
C
Remião
F
F
Duarte
J A
JA
Navarro
A Sánchez
AS
Bastos
M L
ML
Carvalho
F
F
D000818:Animals; D002374:Catalase / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005979:Glutathione Peroxidase / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D015227:Lipid Peroxidation; D008168:Lung / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D016328:NF-kappa B / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010269:Paraquat / Q000633:toxicity*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012980:Sodium Salicylate / Q000494:pharmacology*; D015996:Survival Rate
D006540:Herbicides; D016328:NF-kappa B; D002374:Catalase; D009195:Peroxidase; D005979:Glutathione Peroxidase; D010269:Paraquat; D012980:Sodium Salicylate