Comparison of γ-glutamyl transferase induction by phenobarbital in the rat, guinea pig and rabbit

Abstract

Serum and hepatic γ-glutamyl transferase (GGT) activities were correlated with the microsomal markers cytochrome P-450 and aminopyrine N-demethylase after i.p. injection of phenobarbital (PB) to rats, guinea pigs and rabbits. The response to PB in the regimen employed was greatest in the rabbit and least in the guinea pig. Great disparities were observed in the microsomal protein contents following PB administration to the three species, masking the responses of the other indices when these were related to protein contents rather than to tissue weights. The increased hepatic GGT activities in PB-treated guinea pigs and rabbits were reflected in increased serum activities of this enzyme; the hepatic and serum GGT activities showed an excellent correlation with cytochrome P-450 and aminopyrine N-demethylase activities, supporting the view that the changes in GGT activity were related to enzyme induction. Although hepatic GGT activity in PB-treated rats also showed good correlation with enzyme induction indices, activity of this enzyme in rat serum was undetectable in control and PB-treated animals. Analysis of ribosome-free microsomal proteins by sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis confirmed the marked increase in three bands in the PB-treated rat, but quite different changes were noted in the guinea pig and the rabbit. Our results extend knowledge about the heterogeneous response to PB shown by different animal species. The data provide further evidence that GGT is a PB-inducible enzyme, and suggest that the rabbit is the best model for elucidating the relationship between enzyme induction and GGT activity occurring in several human clinical situations.