Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)


Pharmaceutical Sciences

First Advisor

Dr. George C. Fuller


Phenobarbital pretreatment significantly enhanced the rise in SGOT and SGPT immediately following a three-hour exposure of rats to carbon tetrachloride by inhalation. However, these parameters of hepatotoxicity were significantly l ower in rats pretreated with .)-.methylcholanthrene when compared to rats pretreated with vehicle and exposed to carbon tetr achloride vapor. Levels of hepatic microsomal. NADPH cytochrome .£ reductase and CO-binding pigment were elevated by phenobarbital pretreatment, but .)-.methylcholanthrene had no effect on hepatic microsomal NADPH cytochrome .£ reductase. Although carbon tetrachloride exposure reduced CO-binding pigment content by 61 per cent in phenobarbital pretreated and by 39 per cent in J-methylcholanthi"ene ·pretreated rats, microsomal NADPH cytochrome .£ reductase wa.s reduced by only 6 per cent and 20 per cent, respectively. In phenobarbital pr~trea.ted rats, exposure to carbon tetrachloride produced a greater decrease in aminopyrine demethylase act i vity than in saline treated carbon tetrachloride exposed controls. However, in J-meteyleholanthrene pretreated rats, exposure to carbon tetrachloride produced a lesser decrease in p..nitroa.nisole demethylase aetivity than in corn oil treated controls. Twenty-one hours after exposure, the difference in SGOT and SGPT values of the phenobarbital and 3- met}\ylcholanthrene pretreated rats wa.s more divergent. Histological evidence at this time period revealed extensive damage in the phenobarbital pretreated. animals and a effect in the J-methylcholanthrene pretreated animals.

While phenobarbital pretreatment enhanced the microsomal diene conjugation absorption indicative of lipid peroxida.tion following carbon tetrachloride exposure, )-methylcholanthrene pretreatment had the opposite effect. Carbon monoxide, but not hypoxia, enhanced the increase in OOOT, stPT, and microsomal diene conjugation absorption following exposure to carbon tetrachloride. These data suggest that the differential effects of J-methylcholanthrene and phenobarbital pretreatment on NADPH cytochrome .2. reductase and CO-binding pigment ~ be responsible for the observed protective effect of J-methylcholanthrene in carbon tetrachloride exposed rats.