کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2580461 1561625 2014 22 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Refined biokinetic model for humans exposed to cobalt dietary supplements and other sources of systemic cobalt exposure
ترجمه فارسی عنوان
مدل بیوشیمیایی تصفیه شده برای افرادی که در معرض مکمل های غذایی کبالت و سایر منابع آفتاب سیستماتیک کبالت قرار دارند
کلمات کلیدی
کبالت، سینتیک گلبولهای قرمز، اتصال آلبومین، دفع کلیوی، جذب کلیه، سم زدایی
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی


• Updated human biokinetic model was developed for Co based on human dosing studies.
• Plasma protein binding, RBC uptake and renal excretion of free Co2+ were emphasized.
• Model predicts blood, plasma, urine, liver, kidney and whole body Co concentrations.
• The model should be useful for dose–response evaluations of exposed populations.

An updated biokinetic model for human exposures to cobalt (Co) was developed based on a comprehensive set of human pharmacokinetics data collected from five male and five female volunteers who ingested ∼1 mg Co/day of a Co supplement for 3 months. Three key experimental observations from the human dosing studies were incorporated into the model: (1) an increase in the measured fraction of large molecular serum protein bound Co from 95% during dosing to 99% after dosing; (2) a linear decrease in Co red blood cell concentration after dosing; and (3) Co renal clearance consistent with estimated glomerular filtration rates and free Co2+ concentration. The model was refined by adding compartments accounting for (1) albumin bound Co in intravascular fluid (serum); (2) albumin bound Co in extravascular fluid with physiologic exchange rates of albumin bound Co between extravascular and intravascular fluid; and (3) a novel sequential cascade of compartments representing red blood cell ages between 1 and 120 days. Reasonable agreement between the modeled and measured urine, serum, and whole blood concentrations were observed (r > 0.84, slope = 0.79–1.0) with gastrointestinal absorption rates between 9% and 66%. In addition, model predictions agreed well with data from several external studies representing healthy human volunteers, dialysis patients, anephric patients, a Co-poisoning incident and whole body retention studies. Our revised model considerably improves the state of knowledge on human Co kinetics, and should be helpful for evaluating elevated blood Co concentrations in currently exposed populations, such as metal-on-metal (MoM) hip implant patients.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 216, 5 June 2014, Pages 53–74
نویسندگان
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