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1 Introduction Methotrexate (MTX) is a dihydrofolate reductase inhibitor and chemotherapeutic agent with proven efficiency against cancers and rheumatoid arthritis ( Oxidative stress, which results from the excess production of reactive oxygen species (ROS), has a fundamental role in the MTX-associated toxicities pathogenesis ( The endoplasmic reticulum (ER) is a fundamental cellular organelle responsible for the newly synthesized proteins folding into their final 3-dimentional structures, post-translational modification, transportation, and quality control ( Apoptosis is essential in cellular homeostasis maintenance and is activated during adverse conditions (Figure 1)

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This solution was sterile filtered through a 0.2 filter and slowly added to a stirred diethylether (50 ml)