Statement of Problem:
Methotrexate is a widely used chemotherapeutic agent known for its efficacy in treating various types of cancer and autoimmune diseases. However, one of the major drawbacks of methotrexate therapy is its neurotoxic side effects, which have been linked to the down regulation of antioxidant enzymes and pathways in the central nervous system. The neurotoxicity of methotrexate can lead to cognitive impairments, peripheral neuropathy, and other serious neurological complications in patients undergoing treatment.
Several studies have reported that methotrexate treatment can disrupt the balance of oxidative stress and antioxidant defense mechanisms in the brain, leading to increased levels of reactive oxygen species (ROS) and decreased levels of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx). These changes in antioxidant status can contribute to the development of neurotoxicity associated with methotrexate therapy.
Furthermore, the down regulation of antioxidant pathways by methotrexate may also compromise the ability of the central nervous system to protect against oxidative damage and inflammation, ultimately exacerbating neuronal injury and dysfunction. Understanding the underlying mechanisms by which methotrexate suppresses antioxidant defense mechanisms in the brain is crucial for developing strategies to mitigate its neurotoxic effects and improve the safety and tolerability of methotrexate therapy.
In this study, we aim to investigate the impact of methotrexate on antioxidant down regulation in the central nervous system and its role in mediating neurotoxicity. By elucidating the molecular mechanisms underlying methotrexate-induced oxidative stress and antioxidant depletion, we hope to identify potential therapeutic targets for preventing or ameliorating the neurotoxic side effects of methotrexate treatment.
References:
1. Salim S, Nguyen P, Nasiripour S, et al. Methotrexate neurotoxicity and antioxidant defenses in the developing brain: role of mitochondria and microglia. Front Cell Neurosci. 2017;11:183.
2. Alizadeh AM, Khaniki M, Azizian S, Mahdavill A. Methotrexate-induced neurotoxicity and cognitive impairment is associated with oxidative stress and down-regulation of antioxidant enzymes in the rat brain. Neurotoxicology. 2015;49:1-8.
3. Grimm EA, Sikora AG, Ekmekcioglu S. Molecular pathways: inflammation-associated nitric-oxide production as a cancer-supporting redox mechanism and a potential therapeutic target. Clin Cancer Res. 2013;19(20):5557-5563.
Pls write me a good statement of problem about methotrexate neurotoxicity on antioxidant down regulation with good intext citations and references.
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