title

عوامل محافظت کننده میتوکندری و لیزوزومی سمیت سلولی و استرس اکسیداتیو ناشی از سیکلوفسفامید و متوترکسات در لنفوسیت های خون انسان را بهبود می بخشد

سلیمی, احمد and پیرهادی, رضوان and جمالی, ژاله and رمضانی, مارال and یوسف ثانی, بهاره السادات and پوراحمد, جلال (1398) عوامل محافظت کننده میتوکندری و لیزوزومی سمیت سلولی و استرس اکسیداتیو ناشی از سیکلوفسفامید و متوترکسات در لنفوسیت های خون انسان را بهبود می بخشد. Human and Experimental Toxicology ــ . pp. 1-9. شاپا 0960-3271 (In Press)

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Title

Mitochondrial and lysosomal protective agents ameliorate cytotoxicity and oxidative stress induced by cyclophosphamide and methotrexate in human blood lymphocytes

English Abstract

Cyclophosphamide (CYP) and methotrexate (MTX) have been evaluated for their ability to induce toxicity in human peripheral blood lymphocytes (PBLs) and the protective role of mitochondrial and lysosomal stabilizing agents. The potential toxicity effects of CYP and MTX were measured in vitro by cellular parameters assays such as cellular viability, reactive oxygen species (ROS) formation, mitochondrial membrane permeability transition (mitochondrial membrane potential (MMP)) collapse, lysosomal membrane damage, intracellular reduced glutathione (GSH), extracellular oxidized glutathione (GSSG), and lipid peroxidation. Separately, human lymphocytes were treated with concentrations of 0.1, 0.2, 0.4, 0.8, and 1.6 ng/mL for CYP and 1, 2, 5, and 10 mg/mL for MTX for 6 h. Statistical evaluations showed that CYP and MTX significantly decreased the cell viability at the three highest concentrations when compared with both the negative and solvent controls. In addition, CYP and MTX were significantly induced ROS formation, MMP collapse, lysosomal membrane damage, lipid peroxidation, and GSH depletion compared with the controls. Mitochondrial and lysosomal protective agents like cyclosporine A and chloroquine, respectively, decreased cytotoxicity and oxidative stress induced by CYP and MTX. The present results indicate that CYP and MTX are toxic to human PBLs and their toxicity could be ameliorated by mitochondrial and lysosomal protective agents.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :احمد سلیمی
دانشجو :رضوان پیرهادی
نویسنده :ژاله جمالی
نویسنده :مارال رمضانی
نویسنده :بهاره السادات یوسف ثانی
نویسنده مسئول :جلال پوراحمد
Additional Information:2018 Impact Factor: 2.171 Indexed in: ISI/Science Citation Index, PubMed/Medline, Embase, Chemical Abstracts Service(CAS) , BIOSIS Previews , Index Medicus
Uncontrolled Keywords:سیکلوفسفامید ، متوترکسات ، سمیت سلولی، سیتوستاتیک ، لنفوسیتهای انسانی
کلیدواژه ها (انگلیسی):Cyclophosphamide, methotrexate, cytotoxic, cytostatic, human lymphocytes
Subjects:QV pharmacology > QV 600 Toxicology
QV pharmacology
Divisions:School of Pharmacy > Department of Toxicology
ID Code:12151
Deposited By: دکتر احمد سلیمی
Deposited On:11 Jun 1398 13:25
Last Modified:11 Jun 1398 13:31

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