کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5859510 | 1562353 | 2013 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Physiologically based toxicokinetics of serum aflatoxin B1-lysine adduct in F344 rats
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کلمات کلیدی
SPEGSTCYP450AFB1 - AFB 1DMSO - DMSOHCC - HCCAflatoxin B1 - آفلاتوکسین B1Solid phase extraction - استخراج فاز جامدBiomarker - بیومارکرToxicokinetics - تاکسیکوسینتیک، تاکسیکوکینتیکDimethyl sulfoxide - دیمتیل سولفواکسیدcytochrome P-450 - سیتوکروم P-450Hepatocellular carcinoma - کارسینوم هپاتوسلولار(کارسینوم سلولهای استخوانی)high performance liquid chromatography - کروماتوگرافی مایع با کارایی بالاHPLC - کروماتوگرافی مایعی کاراglutathione S transferase - گلوتاتیون S transferase
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Aflatoxin B1-lysine adduct (AFB-Lys) is a reliable biomarker for aflatoxin exposure; however, a systematic toxicokinetic evaluation has not been reported. In this study, male F344 rats were orally exposed to single, or repeated, doses of AFB1 and the toxicokinetics of serum AFB-Lys that followed treatments were investigated. A single-dose of AFB1 increased serum AFB-Lys levels rapidly peaking at 4 h, followed by first-order elimination, through which the half-life was estimated to be 2.31 days. A physiologically based pharmacokinetic model showed that approximately 3.00-3.90% and 1.12-1.98% of the administered AFB1 doses were converted to serum AFB-Lys adducts at 2 h and 24 h post treatment, respectively. Repeated AFB1 exposure at 5-25 μg/kg body weight linearly increased serum AFB-Lys levels for 5 weeks in animals, resulting in a 1-1.5 times higher AFB-Lys level overall. This indicates the potential of this adduct as a reliable biomarker for repeated low dose exposure. Higher dose exposure at 75 μg/kg increased the level of AFB-Lys to a maximum at 2 weeks, followed by a gradual decrease to near plateau level up to 5 weeks. In conclusion, this study systematically evaluated the toxicokinetics of serum AFB-Lys adduct in F344 rats using a physiologically based pharmacokinetic model and robust statistical modeling analysis and provided a firm and clear understanding of the toxicokinetics of this biomarker.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 303, 7 January 2013, Pages 147-151
Journal: Toxicology - Volume 303, 7 January 2013, Pages 147-151
نویسندگان
Guoqing Qian, Lili Tang, Franklin Wang, Xia Guo, Michael E. Massey, Jonathan H. Williams, Timothy D. Phillips, Jia-Sheng Wang,