Induction of Peroxisomal Enzymes by a Tetrazole-Substituted 2-Quinolinylmethoxy Leukotriene D4 Antagonist

The induction of hepatic peroxisomal /3-oxidation and the peroxisomal bifunctional enzyme (PBE) by the tetrazole-substi-tuted leukotriene D4 receptor antagonist RG 7152 was evalu-ated in vivo following subchronic treatment in the mouse, rat, guinea pig, dog, and rhesus monkey. The ability of RG 7152 to induce this enzyme system in rat extrahepatic tissues reported to respond to peroxisome proliferators and in vitro in primary rat hepatocytes was also investigated. Western blot analysis for PBE and /9-oxidation assays revealed significant induction by RG 7152 in liver homogenates from rats and mice with a lesser effect in guinea pigs and monkeys and no effect in dogs. The degree of induction in rat liver was less than that observed in a positive control group treated with clofibrate (CF). There was slight induction of PBE in rat kidney and small intestine by CF, whereas RG 7152 elicited a minimal response in the kidney an