Lithium Associated Side Effects and Neurotoxicity: Is Lithium Neurotoxicity Related to Iron Deposition?

Abstract

Lithium is a mood stabilizer that Australian psychiatrist John Cade and the Swiss Baastrup and Schou’s pioneering studies brought in the treatment of bipolar disorder. In current guidelines, it is still consid-ered as first line therapy for acute mania, depression and remission periods. Along with numerous neurotrophic and cytoprotective effects, lithium may rarely cause neurotoxicity. Neuro-toxicity might be related with dose dependent or independent. Mechanism of neurotoxicity has not been identified yet. A possible reason of lithium neurotoxicity is that lithium complicates iron efflux from neurons by inhibiting the tau cascade. Accumulation of iron may increase hydroxyl radical formation, resulting in oxidative neurotoxicity. On the other hand, mechanisms that may alleviate iron deposition should also be considered. This review will address the cardiac and met-abolic side effects of lithium and clinical features and biochemical regimes of neurotoxicity, and its relationship with iron accumulation.

Keywords

• Lithium neurotoxicity,iron accumulation,ceruloplasmin

Lityuma Bağlı Yan Etkiler ve Nörotoksisite: Lityum Nörotoksisitesi Demir Birikimiyle İlgili Olabilir mi?

Öz

Lityum Avustralyalı psikiyatri hekimi John Cade ve İsviçreli Baastrup ve Schou’nun öncü çalışmalarla bipolar bozukluk tedavisine kazandırdığı bir duygudurum dengeleyicidir. Güncel tedavi kılavuzlarında akut mani, depresyon ve remisyon dönemlerinde idame tedaviler için hala altın standart tedavi olarak değerlendirilmektedir. Birçok sitoprotektif ve nörotrofik etkisinin yanı sıra lityum nadiren nörotoksisiteye de neden olabilmektedir. Nörotoksisite doz bağımlı ve dozdan bağımsız biçimde görülebilmektedir. Mekanizması tam olarak anlaşılamamıştır. Olası mekanizmalardan biri lityumun tau kaskadını inhibe etmesiyle beyinde bulunan demirin beyin hücrelerinden çıkışının zorlaşmasına neden olarak demir birikimine neden olmasıdır. Demir birikimi hidroksil radikali üretiminin artmasına neden olur ve sonuçta oksidatif nörotoksisite ortaya çıkarabilir. Ancak demir birikimine karşı düzeneklerinde dikkate alınması gerekir.  Bu gözden geçirme yazısında lityuma bağlı kardiyak ve metabolik yan etkiler ile birlikte lityum nörotoksisitesinin klinik özellikleri, biyokimyasal düzenekleri ve demir birikimi ile ilişkisi incelenmiştir.

Anahtar Kelimeler

• lityum nörotoksisitesi,demir birikimi,serüloplazmin

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