کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5846080 | 1128452 | 2014 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Characterization of acute biliary hyperplasia in Fisher 344 Rats administered the Indole-3-Carbinol Analog, NSC-743380
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
AAALACTIFFPBSGGTBQLNCIα-naphthylisothiocyanateANITSVSSOPALTH&E - H & EIndole-3-carbinol - Indole-3-CarbinolROS - ROSAST - آسپارتات ترانس آمینازAspartate aminotransferase - آسپارتات ترانس آمیناز یا AST Alanine aminotransferase - آلانین آمینوترانسفرازALP - آلکالن فسفاتازAlkaline phosphatase - آلکالین فسفاتاز یا فسفاتاز قلیاییAssociation for Assessment and Accreditation of Laboratory Animal Care - انجمن ارزیابی و اعتباربخشی مراقبت از حیوانات آزمایشگاهیstandard deviation - انحراف معیارImmunohistochemistry - ایمونوهیستوشیمیIHC - ایمونوهیستوشیمیTagged Image File Format - برچسب فایل فرمت تصویرBUN - خوبstandard operating procedure - روش های عملیاتی استانداردHepatotoxicity - سمیت کبدnot applicable - قابل اجرا نیستPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریNational Cancer Institute - موسسه ملی سرطانblood urea nitrogen - نیتروژن اوره خونHematoxylin and Eosin - هماتوکسیلین و ائوزینRat liver - کبد چربgamma glutamyl transferase - گاما گلوتامیل ترانسفرازReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
NSC-743380 (1-[(3-chlorophenyl)-methyl]-1H-indole-3-carbinol) is in early stages of development as an anticancer agent. Two metabolites reflect sequential conversion of the carbinol functionality to a carboxaldehyde and the major metabolite, 1-[(3-chlorophenyl)-methyl]-1H-indole-3-carboxylic acid. In an exploratory toxicity study in rats, NSC-743380 induced elevations in liver-associated serum enzymes and biliary hyperplasia. Biliary hyperplasia was observed 2Â days after dosing orally for 2 consecutive days at 100Â mg/kg/day. Notably, hepatotoxicity and biliary hyperplasia were observed after oral administration of the parent compound, but not when major metabolites were administered. The toxicities of a structurally similar but pharmacologically inactive molecule and a structurally diverse molecule with a similar efficacy profile in killing cancer cells in vitro were compared to NSC-743380 to explore scaffold versus target-mediated toxicity. Following two oral doses of 100Â mg/kg/day given once daily on two consecutive days, the structurally unrelated active compound produced hepatic toxicity similar to NSC-743380. The structurally similar inactive compound did not, but, lower exposures were achieved. The weight of evidence implies that the hepatotoxicity associated with NSC-743380 is related to the anticancer activity of the parent molecule. Furthermore, because biliary hyperplasia represents an unmanageable and non-monitorable adverse effect in clinical settings, this model may provide an opportunity for investigators to use a short-duration study design to explore biomarkers of biliary hyperplasia.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 281, Issue 3, 15 December 2014, Pages 303-309
Journal: Toxicology and Applied Pharmacology - Volume 281, Issue 3, 15 December 2014, Pages 303-309
نویسندگان
Sandy R. Eldridge, Joseph Covey, Joel Morris, Bingliang Fang, Thomas L. Horn, Karen E. Elsass, John R. III, David L. McCormick, Myrtle A. Davis,