کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2581000 | 1130169 | 2011 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Indocyanine green clearance varies as a function of N-acetylcysteine treatment in a murine model of acetaminophen toxicity
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کلمات کلیدی
NACNAPQIICGCLTAPAPALTMRTGSHλzAUC0–∞AUC - AUCN-acetylcysteine - N-استیل سیستئینAST - آسپارتات ترانس آمینازAspartate aminotransferase - آسپارتات ترانس آمیناز یا AST Alanine aminotransferase - آلانین آمینوترانسفرازAcetaminophen - استامینوفن Indocyanine green - ایندوسیانین سبزtotal body clearance - ترخیص کامل بدنPharmacokinetics - فارماکوکینتیکarea under the curve - منطقه تحت منحنیMean residence time - میانگین زمان اقامتHepatocellular necrosis - نکروز سلول های خونیGlutathione - گلوتاتیون
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Standard assays to assess acetaminophen (APAP) toxicity in animal models include determination of ALT (alanine aminotransferase) levels and examination of histopathology of liver sections. However, these assays do not reflect the functional capacity of the injured liver. To examine a functional marker of liver injury, the pharmacokinetics of indocyanine green (ICG) were examined in mice treated with APAP, saline, or APAP followed by N-acetylcysteine (NAC) treatment.Male B6C3F1 mice were administered APAP (200Â mg/kg IP) or saline. Two additional groups of mice received APAP followed by NAC at 1 or 4Â h after APAP. At 24Â h, mice were injected with ICG (10Â mg/kg IV) and serial blood samples (0, 2, 10, 30, 50 and 75Â min) were obtained for determination of serum ICG concentrations and ALT. Mouse livers were removed for measurement of APAP protein adducts and examination of histopathology. Toxicity (ALT values and histology) was significantly increased above saline treated mice in the APAP and APAP/NAC 4Â h mice. Mice treated with APAP/NAC 1Â h had complete protection from toxicity. APAP protein adducts were increased in all APAP treated groups and were highest in the APAP/NAC 1Â h group. Pharmacokinetic analysis of ICG demonstrated that the total body clearance (ClT) of ICG was significantly decreased and the mean residence time (MRT) was significantly increased in the APAP mice compared to the saline mice. Mice treated with NAC at 1Â h had ClT and MRT values similar to those of saline treated mice. Conversely, mice that received NAC at 4Â h had a similar ICG pharmacokinetic profile to that of the APAP only mice. Prompt treatment with NAC prevented loss of functional activity while late treatment with NAC offered no improvement in ICG clearance at 24Â h. ICG clearance in mice with APAP toxicity can be utilized in future studies testing the effects of novel treatments for APAP toxicity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 189, Issue 3, 1 February 2011, Pages 222-229
Journal: Chemico-Biological Interactions - Volume 189, Issue 3, 1 February 2011, Pages 222-229
نویسندگان
Alessandra Milesi-Hallé, Susan M. Abdel-Rahman, Aliza Brown, Sandra S. McCullough, Lynda Letzig, Jack A. Hinson, Laura P. James,