14C标记1,2,7,8-TCDD在鲤体内分布及代谢的初步研究
PRELIMINARY STUDIES ON METABOLISM AND DISTRIBUTION OF14C LABELED 1,2,7,82TETRACH LORODIBENZO2P2DIOXIN IN COMMON CARP
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摘要: 利用14C标记1,2,7,8-四氯代二苯并二噁英(1,2,7,8Tetrachloro[U—14C]dibenzodioxin,14C1,2,7,8TCDD)初步研究了其在鲤体内的分布和代谢规律。14C1,2,7,8-TCDD溶解于丙酮/植物油中,腹腔暴露。暴露1、2、4、8、12d后取样,肝脏、胆汁、腹腔脂肪等消化制样后用液闪仪测量放射性活度。肝脏和胆汁内的放射性活度同步变化,都是第8d达到峰值后下降。腹腔脂肪内1—2d放射性明显高于随后取样的样品。肝和腹腔脂肪的分布量之比呈现“S”型变化趋势。暴露4d后,1,2,7,8-TCDD在鱼体内分布的大小顺序为:脂肪肝脏消化管性腺肾脏脾脏皮肤鳃肌肉脑血液,从分布总量上看脂肪、肝脏、性腺、消化管和肌肉组织是鱼体内分布的主要部位。薄层色谱和放射性自显影以及GC/MS等方法分析了胆汁内的代谢物,并采用不同的溶剂系统来分离了母化合物其代谢产物。结果表明胆汁内母化合物的含量较少,大部分以代谢物形式存在并且胆汁内至少存在3种代谢产物。Abstract: 2,3,7,82 Tetra chlorodibenzo pdioxin(TCDD),an unwanted contaminant of combustion and chlorine bleaching processes,is the most toxic member of the halogenated aromatic hydrocarbons. The disposition and pharmacokinetics of 2,3,7,82 tetra chlorodibenzo pdioxin(TCDD) has been investigated in several species and under various exposure conditions but veryfew studiesare about its metabolites because of its high stability. The distribution profile and metabolism fate of 1,2,7,82 Tetra chloro [U2.4C]dibenzodioxin in carp Cyprinus carpio were studied in this paper.1,2,7,82TCDD was dissolved in acetone/corn oil(8/95,v/v) and administrated by a single intraperitoneal injection(i.p,46.4 μ Ci kg-1bodyweight). Liver,bile and visceral fat were sampled at 1,2,4,8,12 days after the exposure and the radioactivities in those sample was assayed by liquid scintillation counter.100mg tissue or 100 μ L bile in little flask was mixed with 0.2mL perchloric acid,0.3mL hydrogen peroxide and was put into a heatingoven 75 ℃for an hour. 10mL scintillation liquid was addedinto the flask immediately after the digest and bleaching procedure. The remanent bile was collected and stored in-80 ℃formetabolite studies.The radioactivity in liver and bile increased in the first 8 days and decrease sequently. The radioactivity in visceral fat washigh obviously in the first 2 days and then decreased. Time course of liver to visceral fat ratio of percent of administered dose exhibited an apparent “S” pattern which shows 1,2,7,82TCDD was transferredfrom visceral fat to liver in the first 8 days. The con2centrations of 1,2,7,82TCDD in various organs sampled at 4 days have much difference:visceral fat > liver > gastrointestinal tract> gonad > kidney > spleen > skin > gill > muscle > brain > blood. Visceral fat,liver,gonad,gastrointestinal tract and muscle werethe main disposition sites of 1,2,7,82TCDD. The metabolites in bile were studied by thin layer chromatogram,radioautographand GC/MS. Various solvent systems had been developed to separate the parent compound and its metabolites. The Ethylacetate/Acetonitrile/Acetic acid (10:2:0.2) is better to separate the metabolites than other solvent systems such asDichloromethane,Hexane/Ethyl acetate (2:1),Ethyl acetate/Aceton/Acetic acid(10:2:0.1) and Acetone/Acetonitrile/Water(4:2:1). The results show that it exists at least 3 kinds of metabolite in bile,and the parent compound identified by GC/MS isonly a small portion of radioactive materials.
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Keywords:
- Dioxin /
- Common Carp /
- Distribution /
- Biotransformation
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