کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5817074 | 1116470 | 2016 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pathogenetic analyses of carbamazepine-induced liver injury in F344 rats focused on immune- and inflammation-related factors
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کلمات کلیدی
DAMPsGATA-3CyPGSHHO-1CbzALTMCP-1APAPTLRRORTGFFOXP3BSOHeme oxygenase-1MIP-2T helperTNFROS - ROSAdenosine Triphosphate - آدنوزین تری فسفاتATP - آدنوزین تری فسفات یا ATPDrug-induced liver injury - آسیب کبدی ناشی از مواد مخدرAlanine aminotransferase - آلانین آمینوترانسفرازAcetaminophen - استامینوفن inflammation - التهاب( توروم) damage-associated molecular patterns - الگوهای مولکولی مرتبط با آسیبimmunoglobulin - ایمونوگلوبولینinterleukin - اینترلوکینtransforming growth factor - تبدیل فاکتور رشدELISA - تست الیزاEnzyme-linked immunosorbent assay - تست الیزاPreclinical testing - تست پیش از موعدT-bet - تی شرط بندیToll-like receptor - تیالآرforkhead box P3 - جعبه جعبه P3cluster of differentiation - خوشه تمایزreverse transcription - رونویسی معکوسKupffer cell - سلول کوپفرCytochrome P450 - سیتوکروم پی۴۵۰T-box transcription factor - فاکتور رونویسی T جعبهtumor necrosis factor - فاکتور نکروز تومورmacrophage inflammatory protein-2 - ماکروفاژ التهابی پروتئین -2Rat - موش صحراییcarbamazepine - کاربامازپینGlutathione - گلوتاتیونReactive oxygen species - گونههای فعال اکسیژنRetinoic acid-related orphan receptor - گیرنده یتیم وابسته به اسید رتینوئیک
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم کشاورزی و بیولوژیک
علوم دامی و جانورشناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Pathogenetic analyses of carbamazepine-induced liver injury in F344 rats focused on immune- and inflammation-related factors Pathogenetic analyses of carbamazepine-induced liver injury in F344 rats focused on immune- and inflammation-related factors](/preview/png/5817074.png)
چکیده انگلیسی
Drug-induced liver injury is one of the major reasons for a drug to be withdrawn postmarketing. Carbamazepine (CBZ), an anticonvulsant agent, has been reported rarely to cause liver failure in humans. We recently generated a rat model of CBZ-induced liver injury using F344 rats for five consecutive days of CBZ administration combined with a glutathione (GSH) depletor, l-buthionine S,R-sulfoximine, treatment. The involvement of metabolic activation was demonstrated in developing CBZ-induced liver injury, and a difference in metabolic activation reactions between mice and rats was indicated. In this study, we analyzed the pathogenetic mechanism of CBZ-induced liver injury, primarily focusing on immune- and inflammation-related factors using the rat model for CBZ-induced liver injury. After the last CBZ administration, plasma alanine aminotransfearase (ALT) levels were drastically increased. In the histopathological evaluation, time-dependent hepatocellular degeneration and necrosis were observed in the centrilobular region. Different from mice, although hepatic mRNA expression levels of inflammation-related genes were increased, T-helper cell-related genes were not predominantly changed in rats. The number of ED1- and ED2-positive macrophages was increased in injured centrilobular areas in the liver with CBZ-induced liver injury. Treatment with a Kupffer cell depletor, gadolinium chloride, prevented the elevation of plasma ALT levels and an increase in the hepatic mRNA expression levels of inflammation-related genes. Hepatic adenosine triphosphate (ATP) contents were significantly decreased 24Â h after CBZ administration. Therefore, the Kupffer cells-mediated inflammation was predominant in the development of the CBZ-induced liver injury in rats.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental and Toxicologic Pathology - Volume 68, Issue 1, January 2016, Pages 27-38
Journal: Experimental and Toxicologic Pathology - Volume 68, Issue 1, January 2016, Pages 27-38
نویسندگان
Eita Sasaki, Azumi Iida, Shingo Oda, Koichi Tsuneyama, Tatsuki Fukami, Miki Nakajima, Tsuyoshi Yokoi,