Toxicity Evaluation of 6-Mercaptopurine Using Accelerated Cytotoxicity Mechanism Screening (ACMS) techniques

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SALIMI AHMAD; Rahmandoost Melina; POURAHMAD JALAL

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Journal Paper

Paper Information

Journal: IRANIAN JOURNAL OF PHARMACEUTICAL SCIENCES Year:2016 | Volume:12 | Issue:3 Page(s): 65-74

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Title

Toxicity Evaluation of 6-Mercaptopurine Using Accelerated Cytotoxicity Mechanism Screening (ACMS) techniques

Author(s)

SALIMI AHMAD | Rahmandoost Melina | POURAHMAD JALAL | Issue Writer Certificate

Keywords

ACMS

Hepatotoxicity

lysosome

Mercaptopurine

Mitochondria

Reactive Oxygen Species

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 μ M. 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.

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APA: Copy

Rahmandoost, Melina, & POURAHMAD, JALAL. (2016). Toxicity Evaluation of 6-Mercaptopurine Using Accelerated Cytotoxicity Mechanism Screening (ACMS) techniques. IRANIAN JOURNAL OF PHARMACEUTICAL SCIENCES, 12(3), 65-74. SID. https://sid.ir/paper/300419/en

Vancouver: Copy

Rahmandoost Melina, POURAHMAD JALAL. Toxicity Evaluation of 6-Mercaptopurine Using Accelerated Cytotoxicity Mechanism Screening (ACMS) techniques. IRANIAN JOURNAL OF PHARMACEUTICAL SCIENCES[Internet]. 2016;12(3):65-74. Available from: https://sid.ir/paper/300419/en

IEEE: Copy

Melina Rahmandoost, and JALAL POURAHMAD, “Toxicity Evaluation of 6-Mercaptopurine Using Accelerated Cytotoxicity Mechanism Screening (ACMS) techniques,” IRANIAN JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 12, no. 3, pp. 65–74, 2016, [Online]. Available: https://sid.ir/paper/300419/en

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