Carbon tetrachloride (CCl4) levels and serum activities of liver enzymes following acute CCl4 intoxication.

Peak levels of carbon tetrachloride (CCl4) as determined by head-space gas chromatography were observed 3-6 h following an acute oral dose of CCl4 in the blood, liver and fat of rats. Subsequently, there was a rapid decline of CCl4 levels. Conversely, serum activities of enzymes originating from the liver such as glutamate oxalacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and glutamate dehydrogenase (GDH) increased considerably and showed activity peaks between 12-48 h following CCl4 administration, indicating a delayed response of CCl4 on the activity levels of enzymes in the blood.

Effect of ethanol on carbon tetrachloride levels and hepatotoxicity after acute carbon tetrachloride poisoning.

To study the effect of an acute dose of ethanol on carbon tetrachloride (CCl4) concentration and hepatotoxicity, female rats received ethanol (2.5 ml/kg body wt.) either intragastrically or intraperitoneally following intragastric administration of CCl4 (1.5 ml/kg body wt.). Three hours after acute CCl4 intoxication there was a striking increase in CCl4 concentration in animals treated simultaneously with ethanol intragastrically compared to those receiving ethanol intraperitoneally. This increase was significant (P less than 0.05) and amounted to 211% for blood, 236% for liver and 405% for fat tissue, whereas animals treated with CCl4 alone showed CCl4 concentrations in the range between the two other experimental groups. Serum activities of glutamate oxalacetate transaminase, glutamate pyruvate transaminase and glutamate dehydrogenase were found to be considerably higher in animals treated with the combination of CCl4 and ethanol when compared to those receiving CCl4 alone, showing that ethanol given intraperitoneally or intragastrically enhances CCl4 hepatotoxicity. Since the intraperitoneal administration of ethanol led to a reduction rather than an increase in CCl4 concentration in the early phase of intoxication, additional mechanisms independent of actual levels of CCl4, such as direct effects of ethanol on the CCl4 metabolizing enzyme of the membrane of the endoplasmic reticulum, have to be implicated in the pathogenesis of the potentiation of CCl4 hepatotoxicity by ethanol.