Metabolism of sulphobromophthalein II. Species differences between rats, guinea-pigs and rabbits

Author:

Sano Kazumi1,Totsuka Yukari1,Ikegami Yoji1,Uesugi Takashi1

Affiliation:

1. Department of Drug Metabolism and Disposition, Meiji Pharmaceutical University, Kiyose-si, Tokyo 204-8588, Japan

Abstract

Abstract Interesting species differences in the metabolism of sulphobromophthalein sodium have been observed between rats, guinea-pigs and rabbits. The species difference was measured in terms of sulphobromophthalein monoglutathione conjugate (mGSH) positional isomer formation. After an intravenous injection of sulphobromophthalein to rats, 92% of sulphobromophthalein-mGSH excreted into bile was the α -isomer. In contrast, in guinea-pigs the three isomers α, β and δ were excreted in equivalent amounts. In rabbits, the majority of sulphobromophthalein-mGSH was excreted as the β-isomer. The formation ratio of glutathione (GSH) conjugates in-vitro using cytosolic glutathione S-transferases (GSTs) prepared from livers generally accounted for the biliary excretion ratio of α-, β - and δ-monomercaptide isomers in-vivo. GSTs from the livers of rat, guinea-pig, and rabbit were purified and characterized. Although their main GSTs produced different isomers, their 20 amino acid residues showed that they belonged to the same class mu of GSTs. The results suggested differences of the three-dimensional structure of GSTs that formed sulphobromophthalein-mGSH isomers between the three animal species.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Reference27 articles.

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