m-ジクロロベンゼン及びその含硫代謝物のマウス肝薬物代謝酵素系に及ぼす影響

概要

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Sulfur-containing metabolites, 2,4-dichlorophenyl methyl sulfoxide, 2,4-dichlorophenyl methyl sulfone (2,4-DCPSO_2CH_3), 3,5-dichlorophenyl methyl sulfoxide and 3,5-dichlorophenyl methyl sulfone (3,5-DCPSO_2CH_3) were all found in the urine of both male and female mice given orally a 200 mg/kg dose of m-dichlorobenzene (m-DCB). m-DCB (200 mg/kg) given to mice of both sexes by either oral or intraperitoneal (i.p.) route increased the activities of aminopyrine N-demethylase (AD) and aniline hydroxylase, and the content of cytochrome P-450 in the liver microsomes. 3,5-DCPSO_2CH_3 (100μmol/kg, i.p.) induced markedly the enzyme system in mice of both sexes. On the other hand, 2,4-DCPSO_2CH_3 (100 μmol/kg, i.p.) decreased significantly the AD activity in the males and the cytochrome b_5 content in the females. An i.p. administration of m-DCB, 2,4-DCPSO_2CH_3 or 3,5-DCPSO_2CH_3 also caused a marked increase in epoxide hydrolase activity in the livers of the male and female mice, except that 2,4-DCPSO_2CH_3 had no effect on the enzyme activity in the females. Thus, the differences in the effects of 2,4- and 3,5-DCPSO_2CH_3 on the enzyme system were demonstrated and the sex differences in the effects of the sulfones were also found in mice.
公益社団法人日本薬学会の論文
1988-02-28