کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5827336 | 1558922 | 2015 | 17 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The transferability from rat subacute 4-week oral toxicity study to translational research exemplified by two pharmaceutical immunosuppressants and two environmental pollutants with immunomodulating properties
ترجمه فارسی عنوان
انتقال قابل توجهی از سوکسواتریت 4 هفته ای سمیت خوراکی به مطالعه تحلیلی نشان داده شده است که نشان دهنده دو داروی ضد درد دارویی و دو آلاینده محیطی با خواص ایمنی
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کلمات کلیدی
IC90HCBSRBCBFRBAPAZAn.d.CyPOECD TGHEVAH-receptorPAHPFCAPBMCFACScanPlaque forming cell assayEPAH&E - H & Eazathioprine - آزاتیوپرین International Agency for Research on Cancer - آژانس بین المللی تحقیقات سرطانIARC یا International Agency for Research on Cancer - آژانس بین المللی تحقیقات سرطانEnvironmental Protection Agency - آژانس حفاظت از محیط زیستCSA - ایالات مؤتلفهٔ آمریکاHexachlorobenzene - بنزن هگزاکلراید، هگزاکلروبنزنBenzo[a]pyrene - بنزو [a] پییرنELISA - تست الیزاEnzyme-linked immunosorbent assay - تست الیزاThiopurine methyltransferase - تیوپورین متیل ترانسفرازtest guideline - دستورالعمل آزمونFemale - زنPeripheral blood mononuclear cell - سلول تک هسته ای خون محیطیNatural killer cells - سلولهای کشنده طبیعیImmunotoxicology - سم شناسی ایمنیImmunotoxicity - سمیت ایمنیCytochrome P450 - سیتوکروم پی۴۵۰Cyclosporine A - سیکلوسپورینAfigure - شکلFig. - شکل.fluorescence activated cell sorter - فلورسانس سلول فعال شده سلولnot determined - مشخص نشدهICH - منMale - نرHematoxylin and Eosin - هماتوکسیلین و ائوزینPolycyclic aromatic hydrocarbons - هیدروکربن آروماتیک چندحلقهایbody weight - وزن بدنhigh endothelial venules - ونولهای اندوتلیال بالاPALS - پالسInternational Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use - کنفرانس بین المللی هماهنگی الزامات فنی ثبت دارویی برای استفاده انسانیsheep red blood cells - گلبول های قرمز گوسفندaryl hydrocarbon receptor - گیرنده آرویل هیدروکربن
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
چکیده انگلیسی
Exposure to chemicals may have an influence on the immune system. Often, this is an unwanted effect but in some pharmaceuticals, it is the intended mechanism of action. Immune function tests and in depth histopathological investigations of immune organs were integrated in rodent toxicity studies performed according to an extended OECD test guideline 407 protocol. Exemplified by two immunosuppressive drugs, azathioprine and cyclosporine A, and two environmental chemicals, hexachlorobenzene and benzo[a]pyrene, results of subacute rat studies were compared to knowledge in other species particular in humans. Although immune function has a high concordance in mammalian species, regarding the transferability from rodents to humans various factors have to be taken into account. In rats, sensitivity seems to depend on factors such as strain, sex, stress levels as well as metabolism. The two immunosuppressive drugs showed a high similarity of effects in animals and humans as the immune system was the most sensitive target in both. Hexachlorobenzene gave an inconsistent pattern of effects when considering the immune system of different species. In some species pronounced inflammation was observed, whereas in primates liver toxicity seemed more obvious. Generally, the immune system was not the most sensitive target in hexachlorobenzene-treatment. Immune function tests in rats gave evidence of a reaction to systemic inflammation rather than a direct impact on immune cells. Data from humans are likewise equivocal. In the case of benzo[a]pyrene, the immune system was the most sensitive target in rats. In the in vitro plaque forming cell assay (Mishell-Dutton culture) a direct comparison of cells from different species including rat and human was possible and showed similar reactions. The doses in the rat study had, however, no realistic relation to human exposure, which occurs exclusively in mixtures and in a much lower range. In summary, a case by case approach is necessary when testing immunotoxicity. Improvements for the translation from animals to humans related to immune cells can be expected from in vitro tests which offer direct comparison with reactions of human immune cells. This may lead to a better understanding of results and variations seen in animal studies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 759, 15 July 2015, Pages 326-342
Journal: European Journal of Pharmacology - Volume 759, 15 July 2015, Pages 326-342
نویسندگان
Jessica Kemmerling, Ellen Fehlert, C. Frieke Kuper, Christine Rühl-Fehlert, Gisela Stropp, Jack Vogels, Cyrille Krul, Hans-Werner Vohr,