Inductive effect of Telazol(R) on hepatic expression of cytochrome P450 2B in rats

Telazol(R), a 1:1 combination of tiletamine HCl and zolazepam HCl, is an anesthetic and immobilizing agent that has been in use in veterinary medicine and animal field studies for more than a decade. No information is available, however, regarding the effects of Telazol(R), or its constituents, on hepatic cytochromes P450. The purpose of the present study was to assess the effect of Telazol(R) on the rat hepatic cytochrome P450 system. Adult male rats were given a single intraperitoneal injection of Telazol(R) at a dose of 20, 40, 80, or 120 mg/kg body weight (six rats/dose), while control rats received the vehicle only. Animals were killed 24 hr later, and hepatic microsomes were prepared. Treatment with Telazol(R) resulted in dose-dependent increases in benzyloxyresorufin O-dealkylase and testosterone 16 beta-hydroxylase activities. Ethoxyresorufin O-deethylase, p-nitrophenol hydroxylase, and testosterone 6 beta- and 7 alpha-hydroxylase activities were essentially unaltered at all doses of the drug. Densitometric quantitation of immunoblots probed with polyclonal antibody against cytochrome P450 2B1 indicated a 17-fold increase in the hepatic level of cytochrome P450 2B1 for rats treated with the highest dose of Telazol(R). In contrast, the level of cytochrome P450 2B2 was increased slightly but not significantly. In the presence of 0.5 mg of anti-cytochrome P450 2B1 IgG/nmol P450, benzyloxyresorufin O-dealkylase activity was inhibited by 92% in hepatic microsomes prepared from a rat treated with Telazol(R) at a dose of 120 mg/kg compared with only 25% inhibition in hepatic microsomes from a control rat. In Summary, the results demonstrate that Telazol(R) specifically induced expression of the cytochrome P450 2B isozymes in rats.