INCREASED SUSCEPTIBILITY TO CARBON TETRACHLORIDE POISONING IN RAT AFTER PRETREATMENT WITH ORAL PHENOBARBITONE

Pretreatment of rats with phenobarbitone, dissolved in the drinking water, increases their susceptibility to CCl4 poisoning. The median lethal dose (LD50) falls from 3.6 ml CCl4/kg in control animals to 0.5 ml/kg in phenobarbitone pretreated animals. 0.25 ml/kg of CCl4 administered orally produces severe liver damage in phenobarbitone pretreated animals as shown by high liver fat and water content, and high plasma isocitrate dehydrogenase and bilirubin levels. This dose of CCl4 produces only slight damage in control animals. Control animals given 2.5 ml/kg CCl4 have a similar degree of liver damage to that found in phenobarbitone treated animals given 0.25 ml/kg CCl4. Both groups metabolise about 12 mg/kg of the administered CCl4 to CO2, in 6 hr. Phenobarbitone pretreatment increases metabolism of CCl4 to CO2 both in vivo and in vitro. Comparison of CCl4 levels in the blood and liver of pretreated and control animals suggest that the toxic effects cannot be related to the action of unaltered CCl4, and strengthen the view that CCl4 must be metabolised to cause cell damage. The nature of the toxic metabolite remains uncertain. © 1969.