Species- and gender-related differences in amine, alcohol and phenol sulphoconjugations

T. Shiraga Department of Pharmacokinetics and Drug Metabolism, Pharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, 1–6, 2-Chome, Kashima, Yodogawa-ku, Osaka, 532, Japan

K. Iwasaki Department of Pharmacokinetics and Drug Metabolism, Pharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, 1–6, 2-Chome, Kashima, Yodogawa-ku, Osaka, 532, Japan

K. Takeshita Department of Pharmacokinetics and Drug Metabolism, Pharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, 1–6, 2-Chome, Kashima, Yodogawa-ku, Osaka, 532, Japan

H. Matsuda Department of Pharmacokinetics and Drug Metabolism, Pharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, 1–6, 2-Chome, Kashima, Yodogawa-ku, Osaka, 532, Japan

T. Niwa Department of Pharmacokinetics and Drug Metabolism, Pharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, 1–6, 2-Chome, Kashima, Yodogawa-ku, Osaka, 532, Japan

Z. Tozuka Department of Pharmacokinetics and Drug Metabolism, Pharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, 1–6, 2-Chome, Kashima, Yodogawa-ku, Osaka, 532, Japan

T. Hata Department of Pharmacokinetics and Drug Metabolism, Pharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, 1–6, 2-Chome, Kashima, Yodogawa-ku, Osaka, 532, Japan

F. P. Guengerich Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN, 37232-8146, USA

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Abstract

1. Species-, gender- and strain-related differences in amine sulphoconjugations were studied in 105000 g supernatants of liver samples isolated from mouse, rat, guinea pig, rabbit, dog, monkey and man and were compared with those of alcoholic and phenolic compounds. Substrates examined were desipramine (an alkylamine), piperazine and piperidine derivatives (alicyclic amines), aniline (an arylamine), tiaramide and dehydroepi-androsterone (alcoholic compounds) and 2-naphthol (a phenolic compound).

2. Sulphoconjugating activities of alicyclic and aryl-amines and tiaramide varied depending on the animal species, sex and strain used. In all animal species examined, the activity for desipramine was low or negligible but for 2-naphthol was consistently detected and high. Amine sulphoconjugations were higher in rabbit than in other animal species. Dog hepatic 105000 g supernatants exhibited low or neglible activities for amines and tiaramide. Females showed higher sulphoconjugating activities for all substrates in mouse and for amines and tiaramide in rat; males exhibited higher activities for 2-naphthol in rat and monkey and for amines in rabbit; there were no clear sex-related differences in other sulphoconjugations.

3. Among BALB/c, C57BL/6, DBA/2, and AKR mouse strains, the AKR strain showed higher activities towards amines and tiaramide than others.

4. In human liver 105000 g supernatants, sulphoconjugating activities for alicyclic amines, dehydroepiandrosterone, and 2-naphthol were detected. Among them, higher activities were observd in piperazine and phenol sulphoconjugations. There were no sex-related differences in the activities of all substrates examined. Good correlations were observed in activities between alicyclic amine and dehydroepiandrosterone sulphoconjugations.

5. These results indicate that activities of amine and alcohol sulphoconjugations vary considerably depending on the substrate, species, sex and strain but phenol sulphoconjugation is consistently detected in all species examined

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Species- and gender-related differences in amine, alcohol and phenol sulphoconjugations

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Species- and gender-related differences in amine, alcohol and phenol sulphoconjugations

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