کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9017975 | 1128681 | 2005 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Contribution of acetaminophen-cysteine to acetaminophen nephrotoxicity II. Possible involvement of the γ-glutamyl cycle
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Contribution of acetaminophen-cysteine to acetaminophen nephrotoxicity II. Possible involvement of the γ-glutamyl cycle Contribution of acetaminophen-cysteine to acetaminophen nephrotoxicity II. Possible involvement of the γ-glutamyl cycle](/preview/png/9017975.png)
چکیده انگلیسی
Acetaminophen (APAP) nephrotoxicity has been observed both in humans and research animals. Our recent investigations have focused on the possible involvement of glutathione-derived APAP metabolites in APAP nephrotoxicity and have demonstrated that administration of acetaminophen-cysteine (APAP-CYS) potentiated APAP-induced renal injury with no effects on APAP-induced liver injury. Additionally, APAP-CYS treatment alone resulted in a dose-responsive renal GSH depletion. This APAP-CYS-induced renal GSH depletion could interfere with intrarenal detoxification of APAP or its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI) and may be the mechanism responsible for the potentiation of APAP nephrotoxicity. Renal-specific GSH depletion has been demonstrated in mice and rats following administration of amino acid γ-glutamyl acceptor substrates for γ-glutamyl transpeptidase (γ-GT). The present study sought to determine if APAP-CYS-induced renal glutathione depletion is the result of disruption of the γ-glutamyl cycle through interaction with γ-GT. The results confirmed that APAP-CYS-induced renal GSH depletion was antagonized by the γ-glutamyl transpeptidase (γ-GT) inhibitor acivicin. In vitro analysis demonstrated that APAP-CYS is a γ-glutamyl acceptor for both murine and bovine renal γ-GT. Analysis of urine from mice pretreated with acivicin and then treated with APAP, APAP-CYS, or acetaminophen-glutathione identified a γ-glutamyl-cysteinyl-acetaminophen metabolite. These findings are consistent with the hypothesis that APAP-CYS contributes to APAP nephrotoxicity by depletion of renal GSH stores through interaction with the γ-glutamyl cycle.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 202, Issue 2, 15 January 2005, Pages 160-171
Journal: Toxicology and Applied Pharmacology - Volume 202, Issue 2, 15 January 2005, Pages 160-171
نویسندگان
Stephan T. Stern, Mary K. Bruno, Robert A. Horton, Dennis W. Hill, Jeanette C. Roberts, Steven D. Cohen,