Pharmacokinetics of vinylidene chloride in the rat.
نویسندگان
چکیده
The metabolism of inhaled vinylidene chloride in rats represents a balance of biotransformation pathways leading to the formation of a reactive alkylating species which is normally detoxified by conjugation with glutathione. Detoxification of the reactive intermediate formed from inhaled VDC is dependent upon the availability of hepatic glutathione (GSH); as VDC exposure concentrations are increased, the fraction of the dose detoxified by conjugation with GSH decreases markedly, commensurate with depletion of hepatic GSH. This reactive intermediate in the absence of GSH alkylates hepatic macromolecules and causes cell death. Similarly, hepatic GSH plays a vital role in the detoxification of the reactive metabolite formed from inhaled vinyl chloride (VC). However, the dose--response relationships for the utilization of GSH and the accumulation of alkylating metabolites following inhalation exposure to either VDC or VC point to distinct differences which may explain the differing biological activities of the two materials. Finally, preliminary pharmacokinetic data for inhaled VDC in mice indicate an enhanced susceptibility to VDC by virtue of an increased ability for production of alkylating VDC metabolites over that observed in the rat. The importance of these findings in light of recent evidence for a carcinogenic effect of VDC in mice is discussed.
منابع مشابه
Comparative mammalian metabolism of vinyl chloride and vinylidene chloride in relation to oncogenic potential.
Elucidation of the role of vinyl chloride metabolites in the various reaction sequences which comprise the metabolic pathway, including the interaction of reactive metabolities with some purine and pyrimidine residues of target-organ DNA, provides some explanation for the (oncogenic) properties associated with the original substance. Comparative investigation of the biological fate of vinyliden...
متن کاملComparative Pharmacokinetics of Berberine, Palmatine and Jatrorrhizine in Rat Plasma after Oral Administration of Rhizoma coptidis and Zuojinwan Using Liquid Chromatography-Tandem Mass Spectrometry
A selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of berberine, palmatine and jatrorrhizine in rat plasma. Target compounds, together with the internal standard (metronidazole), were extracted from rat plasma samples by protein precipitation with acetonitrile-methanol (1:2, v/v). Chromatography was carried out using a ...
متن کاملComparative Pharmacokinetics of Berberine, Palmatine and Jatrorrhizine in Rat Plasma after Oral Administration of Rhizoma coptidis and Zuojinwan Using Liquid Chromatography-Tandem Mass Spectrometry
A selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of berberine, palmatine and jatrorrhizine in rat plasma. Target compounds, together with the internal standard (metronidazole), were extracted from rat plasma samples by protein precipitation with acetonitrile-methanol (1:2, v/v). Chromatography was carried out using a ...
متن کاملEmbryotoxicity and fetotoxicity of inhaled or ingested vinylidene chloride in rats and rabbits.
Embryotoxicity and Fetotoxicity of Inhaled or Ingested Vinylidene Chloride in Rats and Rabbits. MURRAY, F. J., NITSCHKE, K. D., RAMPY, L. W., AND SCHWETZ, B. A. (1979). Toxicol. App/. Pharmacal. 49, 189-202. The teratogenic potential of inhaled or ingested vinylidene chloride was evaluated in Sprague-Dawley rats and New Zealand white rabbits. Both species were exposed to the test material by in...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Environmental Health Perspectives
دوره 21 شماره
صفحات -
تاریخ انتشار 1977