Potentiated hepatotoxicity from concurrent administration of acetaminophen and allyl alcohol to rats

Female Wistar rats were treated with acetaminophen 3.0 g/kg BW and allyl alcohol 75 microliter/kg BW by gastric tube. Hepatic function, measured as galactose elimination capacity and prothrombin index, was reduced to about 0.40 times control value. Plasma alanine transferase activity was elevated more and earlier after treatment with acetaminophen and allyl alcohol compared to administration of acetaminophen alone. Also prothrombin index was reduced more and earlier from the combination. Hepatic glutathione was depleted to a lower level 3 hr after administration of the combination of toxins, compared to administration of acetaminophen alone, after 6 hr there was no difference. Excretion of acetaminophen metabolites, especially the acetaminophen mercapturate, into urine was not changed from the combination. After administration of the toxic combination histological changes in the liver were minor. The results indicate that the two toxins potentiate each other's action. The potentiation is proposed to be due to prevention of compensatory hyperfunction of non-necrotic liver cells rather than to direct metabolic interaction of the toxins.