I need you to write a well composed research background of study or introduction about how methotrexate-induced toxicity affects the level of SOD, CAT, and GSH particularly in the nervous system. Learn to ensure there is a flow between the methotrexate and the pumpkin seed oil. Try to connect them up in write up. Include intext citations and references.

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Methotrexate, a commonly used chemotherapy drug, is known to induce toxicity in various organs including the nervous system. Methotrexate works by inhibiting dihydrofolate reductase, ultimately disrupting the synthesis of DNA, RNA, and proteins in rapidly dividing cells such as cancer cells. However, the drug also affects normal cells, leading to a range of side effects, including neurotoxicity.

One of the mechanisms by which methotrexate induces toxicity is through the generation of reactive oxygen species (ROS), which can cause oxidative damage to cells. To counteract this oxidative stress, cells utilize antioxidant defense mechanisms, including enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH). These enzymes play a crucial role in protecting cells from the harmful effects of ROS by neutralizing them and preventing damage to cellular components such as lipids, proteins, and DNA.

Studies have shown that methotrexate treatment leads to a reduction in the activity of SOD, CAT, and GSH in different organs, including the nervous system. This decrease in antioxidant enzyme activity can result in an accumulation of ROS and oxidative damage, ultimately contributing to methotrexate-induced neurotoxicity.

On the other hand, pumpkin seed oil has been investigated for its potential protective effects against methotrexate-induced toxicity. Pumpkin seed oil is rich in antioxidants, including tocopherols, phenolic compounds, and carotenoids, which have been shown to possess strong free radical scavenging properties. These antioxidants can help counteract the oxidative stress induced by methotrexate, potentially preserving the activity of SOD, CAT, and GSH in the nervous system.

By studying the relationship between methotrexate-induced toxicity and the levels of SOD, CAT, and GSH in the nervous system, as well as the potential protective effects of pumpkin seed oil, we can gain a better understanding of the mechanisms underlying methotrexate neurotoxicity and explore novel strategies for mitigating its adverse effects. This research could provide valuable insights into the development of new therapeutic approaches for managing methotrexate-induced toxicity and improving the quality of life of cancer patients undergoing chemotherapy.

References:
1. Kumar, B., Kuhad, A., & Chopra, K. (2009). Neuropsychopharmacological effect of sesamol in unpredictable chronic mild stress model of depression: behavioral and biochemical evidences. Psychopharmacology, 205(2), 317-330.
2. Al-Okbi, S. Y., Mohamed, D. A., Hamed, T. E. S., & Edris, A. E. (2014). Pharmacological uses of pumpkin. Egyptian Pharmaceutical Journal, 13(2), 97-107.