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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Al Maruf, Abdullah O'Brien, Peter J. Naserzadeh, Parvaneh Fathian, Rozhina Salimi, Ahmad Pourahmad, Jalal |
| Description | Country affiliation: Canada Author Affiliation: Al Maruf A ( a Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada.); O'Brien PJ ( a Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada.); Naserzadeh P ( b Faculty of Pharmacy , University of Toronto , Toronto , Canada.); Fathian R ( c Faculty of Pharmacy , Shahid Beheshti University of Medical Sciences , Tehran , Iran.); Salimi A ( c Faculty of Pharmacy , Shahid Beheshti University of Medical Sciences , Tehran , Iran.); Pourahmad J ( d Department of Pharmacology and Toxicology , School of Pharmacy, Ardabil University of Medical Science , Ardabil , Iran.) |
| 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 µM)-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. |
| File Format | HTM / HTML |
| ISSN | 01480545 |
| Journal | Drug and Chemical Toxicology |
| e-ISSN | 15256014 |
| Language | English |
| Publisher | Taylor & Francis |
| Publisher Date | 2017-03-16 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Toxicology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Health, Toxicology and Mutagenesis Public Health, Environmental and Occupational Health Toxicology Pharmacology Chemical Health and Safety |
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