Alterations in plasma nitric oxide level and arginase activity during the treatment of bipolar depressive episode

Abstract

Objective: Several studies showed that nitric oxide (NO) plays role in the pathophysiology of bipolar disorder (BD). Arginase might be important in the regulation of NO since both arginase and NO synthase use L-arginine as a common substrate. Although studies generally found increased levels of NO in BD, the picture is less clear for arginase activity. The present study aimed to investigate arginase activity together with NO levels in patients with bipolar disorder-depressed episode (BD-DE) in a prospective design. Method(s): 33 BD-DE patients, diagnosed according to DSM-IV, and 33 age, gender and smoking satus matched healthy volunteer controls were included. Serum NO levels and arginase activities of the patient group were measured before any treatment and compared to that of controls. The patients were then allowed for episode specific naturalistic treatments including pharmacotherapy and electroconvulsive therapy when indicated. NO and arginase levels were evaluated on the 30th day of treatment and clinical outcome was measured by the Hamilton Depression Scale. Results: Pretreatment NO levels and arginase activities of the patients were significantly higher than the healthy volunteers (p<0.001 in both). After 30 days of treatment, both NO levels and arginase activities were decreased (p<0.001), and reached to the volunteers’ levels. There was no significant correlation between plasma arginase and NO levels in either at the beginning or 30th day evaluations. Conclusion(s): Interaction between arginase and NO synthase does not seem to be as simple as just competing for a common substrate. Treatment modalities, clinical improvement of the depressive episode or other factors might be important in the normalization of NO levels and arginase activity.

Keywords

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İki uçlu bozuklukta depresif dönemin tedavisi sırasında plazma nitrik oksit düzeyi ve arginaz aktivitesindeki değişiklikler

Öz

Amaç: Nitrik oksitin (NO) iki uçlu bozukluğun (İUB) patofizyolojisinde rol oynadığı çeşitli çalışmalarda gösterilmiştir. Arginaz ve NO’i sentezleyen NO sentaz enzimleri ortak substrat olarak L-arginini kullanır. Bu nedenle arginaz enziminin aktivitesi NO’in düzenlenmesinde önemli olabilir. Yapılan çalışmalarda İUB’de NO düzeyleri artmış olarak bulunsa da, bu hastalardaki arginaz enzimi aktivitesi ile ilgili tablo halen belirsizdir. Bu çalışmada prospektif olarak iki uçlu bozukluk-depresif epizod (İUB-DE) hastalarında NO seviyeleri ile birlikte arginaz aktivitesinin değerlendirilmesi amaçlanmıştır. Yöntem: DSM-IV’e göre tanı konulan 33 İUB-DE hastası ve bu hastalarla yaş, cinsiyet ve sigara kullanımı yönünden eşleştirilmiş sağlıklı gönüllü kontroller çalışmaya dahil edildi. Hasta grubunda herhangi bir tedavi başlamadan önce serum NO düzeyleri ve arginaz aktiviteleri ölçüldü, bulunan değerler kontrol grubunun sonuçlarıyla karşılaştırıldı. Hastalara doğal döneme özgü tedaviler (farmakoterapi ve gereğinde elektrokonvülzif terapi) uygulandı. NO düzeyleri ve arginaz aktiviteleri tedavinin 30. gününde tekrar değerlendirildi. Klinik sonlanım Hamilton Depresyon Ölçeği ile değerlendirildi. Bulgular: Hastaların tedavi öncesi NO düzeyi ve arginaz aktivitesi sağlıklı gönüllü kontrollerden istatistiksel olarak anlamlı bir biçimde daha yüksekti (ikisi için de p<0.001). 30 günlük tedavi sonrası hem NO düzeyi hem de arginaz aktivitesi düşerek sağlıklı gönüllü kontrollerin seviyesine ulaştı (p<0.001). Başlangıç ve 30. gündeki plazma arginaz aktiviteleri ve NO düzeyleri arasında anlamlı bir ilişki saptanmadı. Sonuç: Arginaz ve NO sentaz arasındaki ilişkinin sadece aynı substrat için yarışmadan ibaret olmadığı düşünülmüştür. Tedavi modaliteleri, depresif dönemin klinik olarak iyileşmesi ve diğer başka faktörler NO düzeylerinin ve arginaz aktivitesinin normalleşmesinde önemli olabilir.

Anahtar Kelimeler

• İki uçlu bozukluk, nitrik oksit, arginaz, depresyon, tedavi

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