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多溴联苯对C57小鼠不同组织中药物代谢酶的影响。

Effect of polybrominated biphenyls on drug metabolizing enzymes in different tissues of C57 mice.

作者信息

Ahotupa M, Aitio A

出版信息

Toxicology. 1978 Dec;11(4):309-14.

PMID:219561
Abstract

Polybrominated biphenyls (PBBs) are structurally very close to polychlorinated biphenyls (PCBs) which are known to be potent inducers of xenobiotic biotransformation reactions. We have studied the effects of 2 industrial PBB-mixtures, "hexabromobiphenyl" (HBB) and "octabromobiphenyl" (OBB), on enzymes catalyzing drug hydroxylation, epoxide hydration, and conjugation reactions in different tissues of C57 mice. The enzyme activities were measured 10 days after a single i.p. injection of PBBs (75 mg/kg). HBB enhanced the activities of hepatic AHH (1.9-fold), ethoxycoumarin deethylase (5.7-fold), epoxide hydratase (1.5-fold), glutathione S-transferase (1.7-fold) and UDP-glucuronosyltransferase (1.5-fold). In the kidney HBB enhanced the activity of UDP-blucuronosyltransferase 1.5-fold. OBB caused in increase in the activities of liver AHH (1.5-fold), ethoxycoumarin deethylase (2.4-fold) and glutathione S-transferase (1.4-fold). A slight increase was also seen in the activity of UDP-glucuronosyltransferase in digitoninactivated liver microsomes of OBB-treated mice. In the kidney OBB caused a slight but statistically significant decrease in glutathione S-transferase activity. Intraperitoneally injected bromobiphenyls had no effects on these drug metabolizing enzymes in the lung of C57 mice. These results were similar to the effects caused by a mixture of PCBs.

摘要

多溴联苯(PBBs)在结构上与多氯联苯(PCBs)非常接近,而多氯联苯是已知的外源性生物转化反应的强效诱导剂。我们研究了两种工业用多溴联苯混合物“六溴联苯”(HBB)和“八溴联苯”(OBB)对C57小鼠不同组织中催化药物羟基化、环氧化物水化和结合反应的酶的影响。在单次腹腔注射多溴联苯(75毫克/千克)10天后测量酶活性。HBB增强了肝脏芳烃羟化酶(AHH)的活性(1.9倍)、乙氧香豆素脱乙基酶(5.7倍)、环氧化物水化酶(1.5倍)、谷胱甘肽S-转移酶(1.7倍)和UDP-葡糖醛酸基转移酶(1.5倍)。在肾脏中,HBB使UDP-葡糖醛酸基转移酶的活性增强了1.5倍。OBB使肝脏AHH的活性增加(1.5倍)、乙氧香豆素脱乙基酶(2.4倍)和谷胱甘肽S-转移酶(1.4倍)。在经OBB处理的小鼠的洋地黄皂苷灭活的肝脏微粒体中,UDP-葡糖醛酸基转移酶的活性也略有增加。在肾脏中,OBB使谷胱甘肽S-转移酶的活性略有下降,但具有统计学意义。腹腔注射溴代联苯对C57小鼠肺中的这些药物代谢酶没有影响。这些结果与多氯联苯混合物所产生的影响相似。

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