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 veterinar y medicine and animal field studies for more than a decade. No informa tion is available, however, regarding the effects of Telazol(R), or it s constituents, on hepatic cytochromes P450. The purpose of the presen t study was to assess the effect of Telazol(R) on the rat hepatic cyto chrome P450 system. Adult male rats were given a single intraperitonea l injection of Telazol(R) at a dose of 20, 40, 80, or 120 mg/kg body w eight (six rats/dose), while control rats received the vehicle only. A nimals were killed 24 hr later, and hepatic microsomes were prepared. Treatment with Telazol(R) resulted in dose-dependent increases in benz yloxyresorufin O-dealkylase and testosterone 16 beta-hydroxylase activ ities. Ethoxyresorufin O-deethylase, p-nitrophenol hydroxylase, and te stosterone 6 beta- and 7 alpha-hydroxylase activities were essentially unaltered at all doses of the drug. Densitometric quantitation of imm unoblots probed with polyclonal antibody against cytochrome P450 2B1 i ndicated a 17-fold increase in the hepatic level of cytochrome P450 2B 1 for rats treated with the highest dose of Telazol(R). In contrast, t he level of cytochrome P450 2B2 was increased slightly but not signifi cantly. In the presence of 0.5 mg of anti-cytochrome P450 2B1 IgG/nmol P450, benzyloxyresorufin O-dealkylase activity was inhibited by 92% i n hepatic microsomes prepared from a rat treated with Telazol(R) at a dose of 120 mg/kg compared with only 25% inhibition in hepatic microso mes from a control rat. In Summary, the results demonstrate that Telaz ol(R) specifically induced expression of the cytochrome P450 2B isozym es in rats.