Systemic Effects of Methotrexate upon the Peripheral Nerve Tissue
Öz
Methotrexate (MTX) is a widely used oncologic drug due to its antineoplastic and anti-inflammatory effects. Although its toxic effects on the central nervous system at high doses have long been known, its effects on the peripheral nervous system are less studied in the literature. This review discusses the systemic effects of MTX on peripheral nerve tissue at histopathological, biochemical, molecular, and behavioral levels. Experimental animal studies have shown that MTX administration leads to impaired nerve conduction, reduced myelin thickness, axonal degeneration, and increased glial activity. Moreover, elevated homocysteine levels due to disrupted folate metabolism, oxidative stress, the release of pro-inflammatory cytokines, and mitochondrial dysfunction are thought to be the main mechanisms underlying MTX-induced neurotoxicity. MTX-related peripheral neuropathies are often irreversible in clinical practice, but early diagnosis and appropriate pharmacological interventions may allow for recovery. This review aims to raise awareness by compiling current data on the effects of MTX on the peripheral nervous system, both in basic science and clinical applications.
Anahtar Kelimeler
drug toxicity, methotrexate, myelopaty, peripheral nerve injury, peripheral neuropaty
Kaynakça
- 1. Pannu AK. Methotrexate overdose in clinical practice. Curr Drug Metab. 2019;20:714-9.
- 2. Gaies E, Jebabli N, Trabelsi S, Salouage I, Charfi R, Lakhal M, et al. Methotrexate side effects: review article. J Drug Metab Toxicol. 2012;3:1-5.
- 3. Mateos MK, Marshall GM, Barbaro PM, Quinn MCJ, George C, Mayoh C, et al. Methotrexate-related central neurotoxicity: clinical characteristics, risk factors and genome-wide association study in children treated for acute lymphoblastic leukemia. Haematologica. 2022;107:635-43.
- 4. Staff NP, Grisold A, Grisold W, Windebank AJ. Chemotherapy-induced peripheral neuropathy: A current review. Ann Neurol. 2017;81:772-81.
- 5. Burgess J, Ferdousi M, Gosal D, Boon C, Matsumoto K, Marshall A, et al. Chemotherapy-Induced Peripheral Neuropathy: Epidemiology, Pathomechanisms and Treatment. Oncol Ther. 2021;9:385-450.
- 6. Apiraksattayakul N, Jitprapaikulsan J, Sanpakit K, Kumutpongpanich T. Potential neurotoxicity associated with methotrexate. Sci Rep. 2024;14:18548.
- 7. Montejo C, Navarro-Otano J, Mayà-Casalprim G, Campolo M, Casanova-Mollá J. Acute lumbar polyradiculoneuropathy as early sign of methotrexate intrathecal neurotoxicity: Case report and literature review. Clin Case Rep. 2019;7:638-43.
- 8. Xu E, Thomas S, Habibi B. Intrathecal Methotrexate-Induced Lumbosacral Polyradiculopathy: A Case Report. Pain Med Case Rep. 2024;8:31-5.
- 9. Lee HS, Jung HJ, Park JE. A Case of Peripheral Neuropathy Combined with Leukoencephalopathy after Injection with Intrathecal Methotrexate and Vincristine. Blood. 2007;110:4348.
- 10. Zhou FH, Yu Y, Zhou XF, Xian CJ. Methotrexate chemotherapy triggers touch-evoked pain and increased CGRP-positive sensory fibres in the tibial periosteum of young rats. Bone. 2015;73:24-31.
