متوتروکسات سبب آسیب میتوکندریایی و خروج سیتوکروم C در هپاتوسیت های کبد رت میشود

المعروف, عبدالله and ابراین, پیتر and ناصر زاده, پروانه and فتحیان, روژینا and سلیمی, احمد and پوراحمد, جلال (1397) متوتروکسات سبب آسیب میتوکندریایی و خروج سیتوکروم C در هپاتوسیت های کبد رت میشود. Drug and Chemical Toxicology ــ 41 (1). pp. 51-61. شاپا 1525-6014

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Official URL: http://www.tandfonline.com/toc/idct20/current


Methotrexate induced mitochondrial injury and cytochrome c release in rat liver hepatocytes

English Abstract

Methotrexate (MTX) is a folic acid antagonist that is widely used to treat a variety of diseases. One of the most serious side effects of MTX therapy is hepatotoxicity. The potential molecular cytotoxic mechanisms of MTX toward isolated rat hepatocytes were investigated using Accelerated Cytotoxicity Mechanism Screening (ACMS) techniques. A concentration and time dependent increase in cytotoxicity and reactive oxygen species (ROS) formation and a decrease in mitochondrial membrane potential (MMP) were observed with MTX. Furthermore, a significant increase in MTX (300 lM)-induced cytotoxicity and ROS formation were observed when glutathione (GSH)-depleted hepatocytes were used whereas addition of N-acetylcysteine (a GSH precursor) decreased cytotoxicity. Catalase inactivation also increased MTX-induced cytotoxicity, while the direct addition of catalase to the hepatocytes decreased cytotoxicity. MTX treatment in isolated rat mitochondria caused swelling and significantly decreased adenosine triphosphate (ATP) and GSH content, and cytochrome c release. Potent antioxidants such as mesna, resveratrol and Trolox decreased MTX-induced cytotoxicity and ROS formation and increased MMP. This study suggests that MTX-induced cytotoxicity caused by ROS formation and GSH oxidation leads to oxidative stress and mitochondrial injury in rat hepatocytes.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :عبدالله المعروف
نویسنده :پیتر ابراین
نویسنده :پروانه ناصر زاده
نویسنده :روژینا فتحیان
نویسنده مسئول :احمد سلیمی
نویسنده مسئول :جلال پوراحمد
Additional Information:IF: 1.946 Indexed in: ISI, PubMed/Medline, Scopus, EMBASE
کلیدواژه ها (انگلیسی):Hepatotoxicity; reactive oxygen species; glutathione; oxidative stress; mitochondrial injury
Subjects:QV pharmacology > QV 600 Toxicology
QV pharmacology
Divisions:School of Pharmacy > Department of Toxicology
ID Code:8635
Deposited By: Dr Ahmad Salimi
Deposited On:10 Feb 1396 04:09
Last Modified:24 Jan 1401 10:06

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