ارزیابی سمیت 6 مرکاپتوپورین با استفاده از تکنیک ACMS

سلیمی, احمد and رحماندوست, ملینا and پوراحمد, جلال (1395) ارزیابی سمیت 6 مرکاپتوپورین با استفاده از تکنیک ACMS. Iranian Journal of Pharmaceutical Sciences ــ 12 (3). pp. 65-74. شاپا 1735-2444

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Official URL: http://www.ijps.ir/article_23842.html


Toxicity evaluation of 6-mercaptopurine using accelerated cytotoxicity mechanism screening (ACMS) techniques

English Abstract

6- Mercaptopurine (6-MP) is widely used in clinic as an immunosuppressive for treatment of acute lymphocytic leukemia, Crohn’s disease, and ulcerative colitis with documented unpredictable hepatotoxicity. The potential molecular cytotoxic mechanisms of 6-MP against isolated rat hepatocytes were searched in this study using ―Accelerated Cytotoxicity Mechanism Screening (ACMS)‖ techniques. The concentration of 6-MP required to cause 50% cytotoxicity in 2 hour at 37∘C was detected to be 400 µM. A significant increase in 6-MP induced cytotoxicity and reactive oxygen species (ROS) formation, % mitochondrial membrane potential (MMP), lysosomal damage were observed. The addition of chloroquine (lysosomotropic agent), L-carnitine (inhibitor of membrane permeability transition (MPT), Diphenyleneiodonium (DPI) as an inhibitor of production of superoxide, and H2O2 by mitochondria and Dimethyl sulfoxide (DMSO) as a radical scavenger decreased 6-MP-induced cytotoxicity, ROS formation, collapse of MMP, and lysosomal damage. Results from this study suggest that 6-MP-induced cytotoxicity in isolated rat hepatocytes due to ROS formation, mitochondrial and lysosomal damages that resulted in crosstalk toxicity between mitochondrial and lysosomal damage and finally cell death.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :احمد سلیمی
نویسنده :ملینا رحماندوست
نویسنده مسئول :جلال پوراحمد
Additional Information:Indexed in: Scopus, Embase
کلیدواژه ها (انگلیسی):ACMS, Hepatotoxicity, lysosome, Mercaptopurine, Mitochondria, Reactive Oxygen Species.
Subjects:QV pharmacology > QV 600 Toxicology
Divisions:School of Pharmacy > Department of Toxicology
ID Code:8511
Deposited By: Dr Ahmad Salimi
Deposited On:01 Dec 1395 08:28
Last Modified:25 Jan 1401 08:31

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