Effect of ethanol on acute paraquat toxicity in rabbits

The effects of simultaneous administration of ethanol and paraquat on the blood paraquat levels and fatality in rabbits were investigated to evaluate the role of alcohol ingestion in inducing susceptibility to paraquat intoxication. Paraquat alone and with the combination of ethanol were administered orally to rabbits. Rabbit mortality rates for the 24 h period following the ingestion of paraquat alone and paraquat combined with 2.0 and 3.8 g/kg of ethanol, were 0/8, 4/8 and 8/8 subjects, respectively. Animals which ingested paraquat and ethanol at 2.0 and 3.8 g/kg showed significant elevation of blood paraquat levels. Furthermore, an animal dosed with ethanol 2 h following the ingestion of paraquat, consequently, exhibited a marked increase in paraquat levels in the blood 0.5 h after the administration of the ethanol. On the other hand, the average values of Tmax, Cmax, and AUC 8-8 h of paraquat in rabbits dosed simultaneously with paraquat (200 mg/kg) and ethanol, at 2 g/kg, were 1.38 +/- 0.52 h, 28.11 +/- 14.08 micrograms/ml, and 108.97 +/- 39.54 micrograms/ml.h, and at 3.8 g/kg of ethanol, were 2.20 +/- 1.10 h, 47.61 +/- 19.15 micrograms/ml, and 194.43 +/- 53.82 micrograms/ml.h, respectively. These values were significantly higher than those for the rabbits dosed with 200 mg/kg of paraquat alone (Tmax, Cmax, and AUC 0-8 h were 0.94 +/- 0.18 h, 13.81 +/- 2.71 micrograms/ml, and 44.1 +/- 8.6 micrograms/ml.h, respectively). These results show a close correlation between blood paraquat levels in rabbits dosed simultaneously with ethanol and mortality rates.(ABSTRACT TRUNCATED AT 250 WORDS)