Systemic Effects of Methotrexate upon the Peripheral Nerve Tissue

Yıl 2025, Cilt: 34 Sayı: 3, 175 - 183, 30.09.2025

Ozan Işık , Yaşar Barış Turgut , Sümeyra Işik

https://doi.org/10.17827/aktd.1679867

https://izlik.org/JA32BZ76DL

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

Etik Beyan

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Destekleyen Kurum

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Proje Numarası

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Teşekkür

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Metotreksatın Periferik Sinir Dokusu Üzerindeki Sistemik Etkileri

https://izlik.org/JA32BZ76DL

Öz

Metotreksat (MTX), hem antineoplastik hem de antiinflamatuvar etkileri nedeniyle yaygın olarak kullanılan bir onkolojik ilaçtır. Yüksek dozlarda kullanıldığında merkezi sinir sistemi üzerinde toksik etkiler gösterebildiği uzun süredir bilinmesine rağmen, periferik sinir sistemi üzerindeki etkileri literatürde daha az araştırılmıştır. Bu derlemede, MTX’in periferik sinir dokusu üzerine olan sistemik etkileri histopatolojik, biyokimyasal, moleküler ve davranışsal düzeylerde ele alınmıştır. Deneysel hayvan çalışmalarında, MTX uygulamasının sinir iletiminde bozulma, miyelin kalınlığında azalma, aksonal dejenerasyon ve glial aktivitede artışa yol açtığı gösterilmiştir. Ayrıca folat metabolizmasının bozulmasıyla artan homosistein seviyeleri, oksidatif stres, proinflamatuvar sitokinlerin salınımı ve mitokondriyal disfonksiyonun, MTX’e bağlı nörotoksisitenin altında yatan başlıca mekanizmalar olduğu düşünülmektedir. MTX ile ilişkili periferal nöropatiler klinikte çoğu zaman geri dönüşsüz olmakla birlikte, erken tanı ve uygun farmakolojik müdahalelerle iyileşme mümkün olabilmektedir. Bu derleme, MTX’in periferik sinir sistemi üzerindeki etkilerine dair güncel verileri bir araya getirerek, hem temel bilim hem de klinik uygulamalar açısından farkındalık yaratmayı amaçlamaktadır.

Anahtar Kelimeler

drug toxicity , methotrexate , myelopathy , peripheral nerve injuries , peripheral neuropathies

Proje Numarası

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Kaynakça

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