کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2571275 | 1128625 | 2006 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Study of a novel indolin-2-ketone compound Z24 induced hepatotoxicity by NMR-spectroscopy-based metabonomics of rat urine, blood plasma, and liver extracts
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کلمات کلیدی
PChoALTTSPALBGSHTCADmgGlcFIDsGLNCRNTBILTMAOCPMGDMA1H NMR - 1H-NMR2-OG - 2 وCarr–Purcell–Meiboom–Gill - Carr Purcell-Meiboom-GillPCA - PCAfree induction decays - آزاد شدن القاء آزادAST - آسپارتات ترانس آمینازAspartate aminotransferase - آسپارتات ترانس آمیناز یا AST Alanine aminotransferase - آلانین آمینوترانسفرازAlbumin - آلبومینALP - آلکالن فسفاتازAlkaline phosphatase - آلکالین فسفاتاز یا فسفاتاز قلیاییPrincipal components - اجزای اصلیPattern recognition - بازشناخت الگوCho - برایPrincipal components analysis - تجزیه و تحلیل اجزای اصلیFourier transformation - تحول فوریهTrimethylamine-n-oxide - تریمتییلامین-n-اکسیدBUN - خوبdimethylglycine - دی متیل گلیسینDimethylamine - دی متیلامین1H nuclear magnetic resonance - رزونانس مغناطیسی هسته ای -1Relative humidity - رطوبت نسبیphosphatidylcholine - فسفاتیدیل کولینMetabonomics - متابونومیکس urea nitrogen - نیتروژن اورهCitric acid cycle - چرخه اسید سیتریکcreatine - کراتینcreatinine - کراتینینCreatinine kinase - کراتینین کینازtotal bilirubin - کل بیلی روبینCholine - کولینGlu - گلوGlutathione - گلوتاتیونglutamate - گلوتاماتglutamine - گلوتامینGlucose - گلوکزBlood glucose - گلوکز خون یا قند خون
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Antiangiogenic compound has been believed to be an ideal drug in the current cancer biological therapy, but the angiogenesis inhibitors suffer setback for unknown toxicity now. A novel synthetic indolin-s-ketone small molecular compound, 3Z-3-[(1H-pyrrol-2-yl)-methylidene]-1-(1-piperidinylmethyl)-1,3-2H-indol-2-one (Z24) can inhibit angiogenesis in new blood vessels. The hepatotoxicity effects of Z24 oral administration (dosed at 60, 130 and 200Â mg/kg) have been investigated in female Wistar rats by using metabonomic analysis of 1H NMR spectra of urine, plasma and liver extracts, as well as by clinical chemistry analysis, liver histopathology and electron micrographs examination. The 1H NMR spectra of the biofluids were analyzed visually and via pattern recognition by using principal component analysis. The metabonomic trajectory analysis on the time-related hepatotoxicity of Z24 was carried out based on the 1H NMR spectra of urine samples, which were collected daily predose and postdose over an 8-day period. Urinary excretion of citrate, lactate, 2-oxo-glutarate and succinate increased following Z24 dosing. Increased plasma levels of lactate, TMAO and lipid were observed, with concomitant decrease in the level of glucose and phosphatidylcholine. Metabolic profiling on aqueous soluble extracts of liver tissues with the high dose level of Z24 showed an increase in lactate and glutamine, together with a decrease in glucose, glycogen and choline. On the other hand, studies on lipid soluble extracts of liver tissues with the high dose level of Z24 showed increased level in lipid triglycerides and decreased level in unsaturated fatty acids and phosphatidylcholine. Moreover, the most notable effect of Z24 on the metabolism was the reduction in the urinary levels of creatinine and TMAO and the increase in acetate, citrate, succinate and 2-oxo-glutamate with time dependence. The results indicate that in rats Z24 inhibits mitochondrial function through altering the energy and lipid metabolism, which results in the accumulation of free fatty acids and lactate because of the lack of aerobic respiration. These data show that the metabonomic approach represents a promising new technology for the toxicological mechanism study.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 215, Issue 1, 15 August 2006, Pages 71-82
Journal: Toxicology and Applied Pharmacology - Volume 215, Issue 1, 15 August 2006, Pages 71-82
نویسندگان
Quanjun Wang, Ying Jiang, Chunqi Wu, Jianyu Zhao, Shouzhong Yu, Benli Yuan, Xianzhong Yan, Mingyang Liao,