的影响2、3、7、8-tetrachlorodibenzo-p-dioxin或2,2’,4,4’,5、5 ' -hexachlorobiphenyl维生素K-dependent血液凝固在男性和女性摇/ Rij-rats。

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Bouwman CA,面包车大坝E,熔丝公里,Koppe詹,青年社W, Thijssen HH,维米尔C, Van den Berg M

的影响2、3、7、8-tetrachlorodibenzo-p-dioxin或2,2’,4,4’,5、5 ' -hexachlorobiphenyl维生素K-dependent血液凝固在男性和女性摇/ Rij-rats。

臭氧层。1999年2月,38 (3):489 - 505。

PubMed ID

10901669 (在PubMed

]

文摘

新生儿容易出血(新生儿出血性疾病或淬火)由于维生素K缺乏症。诱导细胞色素P450在产妇的胎儿肝脏抗惊厥的治疗,如苯巴比妥、苯妥英被认为是一个主要原因。后期观察增加出血性疾病(方面)在母乳喂养新生儿催生了多氯联苯和二恶英的假说,P450-inducing污染物存在于母乳,可能影响维生素K-dependent凝血。研究了这一假说的老鼠。管理一个单一的口服剂量的0.003,0.03,0.3,3 - 30 nmol 2, 3, 7日8-tetrachlorodibenzo-p-dioxin (TCDD)每公斤体重或0.75,4,20岁,100年或500年micromol 2, 2’, 4, 4’, 5、5 ' -hexachlorobiphenyl /公斤bw (HxCB)雌性和雄性老鼠导致维生素K-dependent凝血因子VII的剂量减少。最高的第七因子减少雌性老鼠为44%,观察后TCDD曝光。最低观察不利影响级别(LOAEL)第七TCDD女性因素水平是0.3 nmol /公斤(96 ng /公斤)。有显著负相关关系第七因子水平和诱导肝ethoxyresorufin O-deethylating (EROD)活动,反映CYP1A1和总P450含量。HxCB没有影响女性凝固的因素。相比之下,在雄性老鼠只有接触HxCB,导致主要CYP2B1和2 b2,减少凝固因素急剧上升到88%。 The LOAEL of HxCB on factor VII in male rats was 100 micromol/kg bw (36 mg/kg). In general, effects on coagulation factors in male rats exceeded those in females. In addition, sex-dependent differences of TCDD and HxCB were observed on the hepatic vitamin K cycle enzyme activities in female and male rats. Vitamin K-dependent (gamma-glutamyl carboxylase activity was mainly induced in female rats; 2.3-fold in the highest dose group of TCDD. In male rats only vitamin K 2,3-epoxide reductase (KO-reductase) activity was induced 1.7-fold by the highest dose of HxCB. KO-reductase activity in female rats was also increased by TCDD, however, less pronounced than the carboxylase activity. Concluding, the hepatic vitamin K cycle still functions and is not blocked by TCDD or HxCB, thus explaining the observed reduction in factor VII. Finally, the possible role of P450 in vitamin K deficiency is discussed. Based on these results it is suggested to investigate the possible role of PCBs and dioxin-like compounds in LHD in more detail.

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药物靶点

药物	目标	类	生物	药理作用	行动
凝血因子VIIa重组人类	维生素K-dependent gamma-carboxylase	蛋白质	人类	未知的	不可用	细节