An in vitro study of the ameliorative role of α-tocopherol on methotrexate-induced oxidative stress in rat heart mitochondria.

Background: Methotrexate (MTX) is a folic acid antagonist widely used as a cytotoxic chemotherapeutic agent for many malignancies. Its use is limited due to wide-ranging toxicities. MTX generates reactive oxygen species. Here, we investigated the efficacy of vitamin E supplementation on MTX-induced alterations in vitro.

Methods: Rat heart mitochondria were isolated and used to assess the extent of swelling, lipid peroxidation and alterations in mitochondrial-specific enzyme activities caused by the addition of 80 μM MTX in the presence and absence of 1.2 μM vitamin E. Control for both groups was maintained.

Result: MTX substantially affects mitochondrial function by increasing lipid peroxidation and mitochondrial swelling. Significant losses in the activities of the tricarboxylic acid cycle enzymes, complex I, II and IV, and an increase in the activity of calcium ATPase were observed in MTX-treated rat mitochondria. Enrichment of the media with vitamin E led to a reduction in swelling and restoration of enzyme activities.

Conclusions: The present study suggests that vitamin E plays a vital role in suppressing MTX-induced mitochondrial toxicity, and affords protection either by reversing the decline of antioxidants or by direct scavenging of free radicals.