Increased UDP-Glucuronosyltransferase Activity in the Liver Butylated Hydroxyanisole and Butylated Hydroxytoluence-Treated Rats

Butylated hydroxyanisole(BHA) has been shown to decrease the toxicological and carcinogenic potential of a variety of chemicals. One possible mechanism for chemoprotection is that BHA increases intestinal UDP-glucronosyltransferase activity and thereby enhances the elimination of the toxicants. Given that I.P injection is major route of xenobiotic exposure, we have investigated the action of BHA and BHT on glucuronidation capacity in the liver of rats. Simple injection of BHA(100mg/kg or 200mg/kg) and BHT(100mg/kg or 200mg/kg) produced a significant increase in microsomal glucuronidation. Futhermore, the concentration of UDP-glucuronic acid, the co-substrate required for glucuronidation reaction was increased almost 2-fold. Administration of BHA and BHT also increased UDP-glucose concentration and UDP-glucose dehydrogenase activities approximately 2-fold. These findings show that BHA and BHT administration increase hepatic glucuronidation capacity and suggest that BHA and BHT may enhance the biotransformation of xenobiotics, and hence excretion, of a variety of carcinogen and or toxins is potentially very important.