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大鼠对六氯苯代谢的性别差异及雌性大鼠卟啉症的发展

Sex differences in the metabolism of hexachlorobenzene by rats and the development of porphyria in females.

作者信息

Rizzardini M, Smith A G

出版信息

Biochem Pharmacol. 1982 Nov 15;31(22):3543-8. doi: 10.1016/0006-2952(82)90573-1.

DOI:10.1016/0006-2952(82)90573-1
PMID:7181936
Abstract

Male and female F 344 rats were dosed every other day for 103 days with 50 mumole of hexachlorobenzene (HCB)/kg. Females developed a hepatic porphyria, the urine and liver levels of porphyrins being 40- and 310-fold higher respectively than those of males. Urine was periodically hydrolysed and analysed for the three metabolites pentachlorophenol, 2,3,5,6-tetrachlorobenzene-1,4-diol and pentachlorothiophenol (derived from the mercapturate). The combined urinary excretion of these was greater in females than males, especially during the first 10 weeks. Pentachlorothiophenol was particularly high in female urine. After 103 days this metabolite was slightly less in female faeces than in male's but free hepatic pentachlorothiophenol was 3.6-fold greater. Although total 24 hr excretions of metabolites were higher by females than males and after 7 daily doses of HCB, a difference in this respect was not conclusively proven. However, total pentachlorothiophenol excretion was always significantly greater by females. The male/female ratios for pentachlorophenol and pentachlorothiophenol in bile were identical to those for faeces. Excretion of metabolites by both adult males and females was stimulated by pretreatment with diethylstilboestrol (DES). No sex differences in metabolism were observed with immature rats.

摘要

将雄性和雌性F344大鼠每隔一天给予50微摩尔/千克的六氯苯(HCB),持续103天。雌性大鼠出现了肝性卟啉症,卟啉的尿液和肝脏水平分别比雄性高40倍和310倍。尿液定期水解,并分析三种代谢物五氯苯酚、2,3,5,6 - 四氯苯 - 1,4 - 二醇和五氯硫酚(来自硫醚氨酸盐)。这些物质的尿液排泄总量在雌性中比雄性中更高,尤其是在最初的10周内。五氯硫酚在雌性尿液中特别高。103天后,这种代谢物在雌性粪便中的含量略低于雄性,但肝脏中游离的五氯硫酚含量是雄性的3.6倍。尽管雌性代谢物的24小时排泄总量高于雄性,并且在每日给予7次HCB后,在这方面的差异尚未得到确凿证实。然而,五氯硫酚的总排泄量在雌性中总是显著更高。胆汁中五氯苯酚和五氯硫酚的雄/雌比率与粪便中的相同。用己烯雌酚(DES)预处理可刺激成年雄性和雌性大鼠代谢物的排泄。未成熟大鼠未观察到代谢方面的性别差异。

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Sex differences in the metabolism of hexachlorobenzene by rats and the development of porphyria in females.大鼠对六氯苯代谢的性别差异及雌性大鼠卟啉症的发展
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引用本文的文献

1
Metabolism of hexachlorobenzene in humans: association between serum levels and urinary metabolites in a highly exposed population.人类体内六氯苯的代谢:高暴露人群血清水平与尿液代谢物之间的关联。
Environ Health Perspect. 1997 Jan;105(1):78-83. doi: 10.1289/ehp.9710578.
2
Synergism of iron and hexachlorobenzene inhibits hepatic uroporphyrinogen decarboxylase in inbred mice.铁与六氯苯的协同作用抑制近交系小鼠肝脏中的尿卟啉原脱羧酶。
Biochem J. 1983 Sep 15;214(3):909-13. doi: 10.1042/bj2140909.
3
Mechanistic studies of the inhibition of hepatic uroporphyrinogen decarboxylase in C57BL/10 mice by iron-hexachlorobenzene synergism.
铁-六氯苯协同作用对C57BL/10小鼠肝脏尿卟啉原脱羧酶抑制作用的机制研究
Biochem J. 1986 Sep 15;238(3):871-8. doi: 10.1042/bj2380871.
4
Biochemical, morphological and flow-cytometric evaluation of the effects of hexachlorobenzene on rat liver.六氯苯对大鼠肝脏影响的生化、形态学及流式细胞术评估
Cell Biol Toxicol. 1990 Apr;6(2):185-203. doi: 10.1007/BF00249593.