Resveratrol fails to provide prophylactic protection in a rat model of organophosphate poisoning

Yossi Rosman, Shaul Ravfogel, Arthur Shiyovich, Shai Shrot, Nadav Milk, Nimrod Ophir, Michael Aviram, Ishai Nir, Michael Kassirer, Arik Eisenkraft

Paraoxonase-1, an organophosphorous-hydrolyzing enzyme, was shown to provide protection against organophosphates poisoning in vivo. In vitro findings suggest that the phytoalexin resveratrol can elevate paraoxonase-1 levels and thus may provide protection against organophosphate poisoning. This study was conducted to evaluate the effect of prolonged resveratrol intake on paraoxonase-1 levels in rats, and its role as a potential prophylactic treatment in organophosphate poisoning. 30 adult male albino Sprague-Dawley rats were randomly assigned into three groups: rats receiving no resveratrol (Control group, n = 10), rats treated once daily with oral gavage of ethanol only (Sham group, n = 6), and rats treated once daily with oral gavage of resveratrol (50 mg/kg) (Study group, n = 14). Following 2 weeks of feeding, all rats were exposed to 1.4LD50 paraoxon (450 mg/kg, intramuscular; 0.5 ml/kg) and monitored for severity of clinical signs and mortality. Paraoxonase-1 activity level was recorded in the beginning of the study and 2 weeks later, just before exposure to paraoxon. We found a significant decrease in paraoxonase-1 activity levels in all groups compared to baseline levels (p = 0.05), but no significant difference was observed between the study group and the controls (p = 0.7). Following exposure to paraoxon, all animals suffered from severe convulsions and died within minutes. Following resveratrol intake in rats, paraoxonase-1 activity levels decreased. We found no beneficial effects in using resveratrol as a prophylactic medical countermeasure.