Inductive effect of telazol ® on hepatic expression of cytochrome p450 2B in rats

Abstract

Telazol ®, 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 ®, or its constituents, on hepatic cytochromes P450. The purpose of the present study was to assess the effect of Telazol ® on the rat hepatic cytochrome P450 system. Adult male rats were given a single intraperitoneal injection of Telazol ® 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 ® resulted in dose-dependent increases in benzyloxyresorufin O-dealkylase and testosterone 16β-hydroxylase activities. Ethoxyresorufin O-deethylase, P-nitrophenol hydroxylase, and testosterone 6β- and 7α-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 ®. 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 ® 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 ® specifically induced expression of the cytochrome P450 2B isozymes in rats.