Dichlorvos (2,2-dichlorovinyl
dimethyl phosphate,
DDVP) is an organophosphorus (OP)
insecticide and
acaricide extensively used to treat external
parasitic infections of farmed fish. In previous studies we have demonstrated the importance of the
glutathione (GSH) metabolism in the resistance of the European eel (Anguilla anguilla L.) to
thiocarbamate herbicides. The present work studied the effects of the
antioxidant and
glutathione pro-drug N-acetyl-L-cysteine (NAC) on the survival of a natural population of A. anguilla exposed to a lethal concentration of
dichlorvos, focusing on the
glutathione metabolism and the
enzyme activities of
acetylcholinesterase (AChE) and
caspase-3 as
biomarkers of neurotoxicity and induction of apoptosis, respectively. Fish pre-treated with NAC (1 mmol kg(-1), i.p.) and exposed to 1.5 mg l(-1) (the 96-h LC85) of
dichlorvos for 96 h in a static-renewal system achieved an increase of the GSH content, GSH/
GSSG ratio, hepatic
glutathione reductase (GR),
glutathione S-transferase (GST),
glutamate:cysteine ligase (GCL), and gamma-glutamyl
transferase (gammaGT) activities, which ameliorated the
glutathione loss and oxidation, and
enzyme inactivation, caused by the OP
pesticide. Although NAC-treated fish presented a higher survival and were two-fold less likely to die within the study period of 96 h, Cox proportional hazard models showed that hepatic GSH/
GSSG ratio was the best explanatory variable related to survival. Hence, tolerance to a lethal concentration of
dichlorvos can be explained by the individual capacity to maintain and improve the hepatic
glutathione redox status. Impairment of the GSH/
GSSG ratio can lead to excessive oxidative stress and inhibition of caspase-3-like activity, inducing cell death by
necrosis, and, ultimately, resulting in the death of the organism. We therefore propose a reconsideration of the individual effective dose or individual tolerance concept postulated by Gaddum 50 years ago for the log-normal dose-response relationship. In addition, as NAC increased the tolerance to
dichlorvos, it could be a potential
antidote for OP
poisoning, complementary to current treatments.