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Evaluation of Azathioprine-Induced Cytotoxicity in an In Vitro Rat Hepatocyte System
المؤلفون المشاركون
Wan, Luke
Maruf, Abdullah Al
O'Brien, Peter John
المصدر
العدد
المجلد 2014، العدد 2014 (31 ديسمبر/كانون الأول 2014)، ص ص. 1-7، 7ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2014-06-30
دولة النشر
مصر
عدد الصفحات
7
التخصصات الرئيسية
الملخص EN
Azathioprine (AZA) is widely used in clinical practice for preventing graft rejection in organ transplantations and various autoimmune and dermatological diseases with documented unpredictable hepatotoxicity.
The potential molecular cytotoxic mechanisms of AZA towards isolated rat hepatocytes were investigated in this study using “Accelerated Cytotoxicity Mechanism Screening” techniques.
The concentration of AZA required to cause 50% cytotoxicity in 2 hrs at 37°C was found to be 400 μM.
A significant increase in AZA-induced cytotoxicity and reactive oxygen species (ROS) formation was observed when glutathione- (GSH-) depleted hepatocytes were used.
The addition of N-acetylcysteine decreased cytotoxicity and ROS formation.
Xanthine oxidase inhibition by allopurinol decreased AZA-induced cytotoxicity, ROS, and hydrogen peroxide (H2O2) formation and increased % mitochondrial membrane potential (MMP).
Addition of N-acetylcysteine and allopurinol together caused nearly complete cytoprotection against AZA-induced hepatocyte death.
TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl), a known ROS scavenger and a superoxide dismutase mimic, and antioxidants, like DPPD (N,N′-diphenyl-p-phenylenediamine), Trolox (a water soluble vitamin E analogue), and mesna (2-mercaptoethanesulfonate), also decreased hepatocyte death and ROS formation.
Results from this study suggest that AZA-induced cytotoxicity in isolated rat hepatocytes may be partly due to ROS formation and GSH depletion that resulted in oxidative stress and mitochondrial injury.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Maruf, Abdullah Al& Wan, Luke& O'Brien, Peter John. 2014. Evaluation of Azathioprine-Induced Cytotoxicity in an In Vitro Rat Hepatocyte System. BioMed Research International،Vol. 2014, no. 2014, pp.1-7.
https://search.emarefa.net/detail/BIM-467440
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Maruf, Abdullah Al…[et al.]. Evaluation of Azathioprine-Induced Cytotoxicity in an In Vitro Rat Hepatocyte System. BioMed Research International No. 2014 (2014), pp.1-7.
https://search.emarefa.net/detail/BIM-467440
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Maruf, Abdullah Al& Wan, Luke& O'Brien, Peter John. Evaluation of Azathioprine-Induced Cytotoxicity in an In Vitro Rat Hepatocyte System. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-7.
https://search.emarefa.net/detail/BIM-467440
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-467440
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
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