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

Year 2011, Volume: 1 Issue: 1, 1 - 6, 01.01.2011

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.

References

  • 1. Belmaker RH. Medical progress: bipolar disorder. New England Journal of Medicine. 2004;51:476-86. 2. Sies H. Oxidative stress: from basic research to clinical application. Am J Med. 1991;91:31S–38S.
  • 3. Andreazza AC, Kauer-Sant’anna M, Frey BN, Bond DJ, Kapczinski F, Young LT, et al. Oxidative stress markers in bipolar disorder: a meta-analysis. J Affect Disord. 2008;111:135-44.
  • 4. Gergerlioglu HS, Savas HA, Bulbul F, Selek S, Uz E, Yumru M. Changes in nitric oxide level and superoxide dismutase activity during antimanic treatment. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:697–702.
  • 5. Selek S, Savas HA, Gergerlioglu HS, Bulbul F, Uz E, Yumru M. The course of nitric oxide and superoxide dismutase during treatment of bipolar depressive episode. J Affect Disord. 2008;107:89–94.
  • 6. Savas HA, Gergerlioglu HS, Armutcu F. Elevated serum nitric oxide and superoxide dismutase in euthymic bipolar patients: impact of past episodes. World J Biol Psychiatry. 2006;7:51–5.
  • 7. Yanik M, Vural H, Tutkun H, Zoroglu SS, Savas HA, Herken H, et al. The role of the arginine-nitric oxide pathway in the pathogenesis of bipolar affective disorder. Eur Arch Psychiatry Clin Neurosci. 2004;254:43–7.
  • 8. Savas HA, Herken H, Yurekli M, Uz E, Tutkun H, Zoroglu SS, et al. Possible role of nitric oxide and adrenomedullin in bipolar affective disorder. Neuropsychobiology. 2002;45:57–61.
  • 9. Andreazza AC, Cassini C, Rosa AR, Leite MC, de Almeida LM, Nardin P, et al. Serum S100B and antioxidant enzymes in bipolar patients. J Psychiatr Res. 2007;41:523–29.
  • 10. Machado-Vieira R, Andreazza AC, Viale CI, Zanatto V, Cereser Jr V, da Silva Vargas R, et al. Oxidative stress parameters in unmedicated and treated bipolar subjects during initial manic episode: a possible role for lithium antioxidant effects. Neurosci Lett. 2007;421:33–6.
  • 11. Ozcan ME, Gulec M, Ozerol E, Polat R, Akyol O. Antioxidant enzyme activities and oxidative stress in affective disorders. Int Clin Psychopharmacol. 2004;19:89–95.
  • 12. Ranjekar PK, Hinge A, Hegde MV, Ghate M, Kale A, Sitasawad S, et al. Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res. 2003;121:109–22.
  • 13. Kuloglu M, Ustundag B, Atmaca M, Canatan H, Tezcan AE, Cinkilinc N. Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder. Cell Biochem Funct. 2002;20:171-5.
  • 14. Andreazza AC, Frey BN, Erdtmann B, Salvador M, Goncalves CA, Kapczinski F. DNA damage in bipolar disorder. Psychiatry Res. 2007;153:27–32.
  • 15. Schulman H. Nitric oxide: a spatial second messenger. Mol Psychiatry. 1997;2:296-9.
  • 16. Papageorgiou C, Grapsa E, Zerefos N, Stamatelopoulos S, Christodoulou GN. Association of serum nitric oxide levels with depressive symptoms: a study with end-stage renal failure patients. Psychother Psychosom. 2001;70: 216–20.
  • 17. Suzuki E, Yagi G, Nakaki T, Kanba S, Asai M. Elevated plasma nitrate levels in depressive states. J Affect Disord. 2001;63:221–4
  • 18. Srivastava N, Barthwal MK, Dalal PK, Agarwal AK, Nag D, Seth PK, et al. A study on nitric oxide, ß- adrenergic receptors and antioxidant status in the polymorphonuclear leukocytes from the patients of depression. J Affect Disord. 2002;72:45–52.
  • 19. Jenkinson CP, Grody WW, Cederbaum SD. Comparative properties of arginases. Comp Biochem Physiol B Biochem Mol Biol. 1996;114:107–32.
  • 20. Albina JE, Mills CD, Henry WL, Caldwell MD. Temporal expression of different pathways of L-arginine metabolism in healing wounds. J Immunol. 1990;144:3877–80.
  • 21. Huang LW, Chang KL, Chen CJ, Liu HW. Arginase levels are increased in patients with rheumatoid arthritis. Kaohsiung J Med Sci. 2001;17:358–63.
  • 22. Durak I, Ozturk HS, Elgun S, Cimen MYB, Yalcyn S. Erythrocyte nitric oxide metabolism in patients with chronic renal failure. Clin Nephrol. 2001;55:460–4.
  • 23. Jansen A, Lewis S, Cattell V, Cook HT. Arginase is a major pathway of L-arginine metabolism in nephritic glomeruli. Kidney Int. 1992;42:1107–12.
  • 24. Szilagyi K. Serum arginase-activity in manic-depressive illness. Arch Psychiatr Nervenkr. 1971;214:390-8.
  • 25. Elgun S, Kumbasar H. Increased serum arginase activity in depressed patients. Prog Neuro Psychopharmacol. Biol Psychiatry. 2000;24:227–32.
  • 26. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th edition. Washington DC: DSMIV-TR; 2004.
  • 27. Akdemir A, Orsel S, Dağ I, Turkçapar H, Iscan N, Ozbay H. Hamilton depresyon derecelendirme ölçeği (HDDÖ)’nin geçerliliği, güvenilirliği ve klinikte kullanımı. 3P Dergisi. 1996;4:251-9.
  • 28. Koltuksuz U, Irmak MK, Karaman A, Uz E, Var A, Ozyurt H, et al. Testicular NO levels after unilateral testicular torsion/detorsion in rats pretreated with caffeinic acid phenethyl ester. Urol Res. 2000;28:360-3.
  • 29. Silberg G, Ben-Shachar D, Navon R. Genetic analysis of nitric oxide synthase 1 variants in schizophrenia and bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2010;5:1318-28.
  • 30. Kowalski J, Labuzek K, Herman ZS. Flupentixol and trifluperidol reduce secretion of tumor necrosis factor-alpha and nitric oxide by rat microglial cells. Neurochem Int. 2003;43:173-8.
  • 31. Wegener G, Volke V, Harvey BH, Rosenberg R. Local, but not systemic, administration of serotonergic antidepressants decreases hippocampal nitric oxide synthase activity. Brain Res. 2003;959:128-34.

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

Year 2011, Volume: 1 Issue: 1, 1 - 6, 01.01.2011

Abstract

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.

References

  • 1. Belmaker RH. Medical progress: bipolar disorder. New England Journal of Medicine. 2004;51:476-86. 2. Sies H. Oxidative stress: from basic research to clinical application. Am J Med. 1991;91:31S–38S.
  • 3. Andreazza AC, Kauer-Sant’anna M, Frey BN, Bond DJ, Kapczinski F, Young LT, et al. Oxidative stress markers in bipolar disorder: a meta-analysis. J Affect Disord. 2008;111:135-44.
  • 4. Gergerlioglu HS, Savas HA, Bulbul F, Selek S, Uz E, Yumru M. Changes in nitric oxide level and superoxide dismutase activity during antimanic treatment. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:697–702.
  • 5. Selek S, Savas HA, Gergerlioglu HS, Bulbul F, Uz E, Yumru M. The course of nitric oxide and superoxide dismutase during treatment of bipolar depressive episode. J Affect Disord. 2008;107:89–94.
  • 6. Savas HA, Gergerlioglu HS, Armutcu F. Elevated serum nitric oxide and superoxide dismutase in euthymic bipolar patients: impact of past episodes. World J Biol Psychiatry. 2006;7:51–5.
  • 7. Yanik M, Vural H, Tutkun H, Zoroglu SS, Savas HA, Herken H, et al. The role of the arginine-nitric oxide pathway in the pathogenesis of bipolar affective disorder. Eur Arch Psychiatry Clin Neurosci. 2004;254:43–7.
  • 8. Savas HA, Herken H, Yurekli M, Uz E, Tutkun H, Zoroglu SS, et al. Possible role of nitric oxide and adrenomedullin in bipolar affective disorder. Neuropsychobiology. 2002;45:57–61.
  • 9. Andreazza AC, Cassini C, Rosa AR, Leite MC, de Almeida LM, Nardin P, et al. Serum S100B and antioxidant enzymes in bipolar patients. J Psychiatr Res. 2007;41:523–29.
  • 10. Machado-Vieira R, Andreazza AC, Viale CI, Zanatto V, Cereser Jr V, da Silva Vargas R, et al. Oxidative stress parameters in unmedicated and treated bipolar subjects during initial manic episode: a possible role for lithium antioxidant effects. Neurosci Lett. 2007;421:33–6.
  • 11. Ozcan ME, Gulec M, Ozerol E, Polat R, Akyol O. Antioxidant enzyme activities and oxidative stress in affective disorders. Int Clin Psychopharmacol. 2004;19:89–95.
  • 12. Ranjekar PK, Hinge A, Hegde MV, Ghate M, Kale A, Sitasawad S, et al. Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res. 2003;121:109–22.
  • 13. Kuloglu M, Ustundag B, Atmaca M, Canatan H, Tezcan AE, Cinkilinc N. Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder. Cell Biochem Funct. 2002;20:171-5.
  • 14. Andreazza AC, Frey BN, Erdtmann B, Salvador M, Goncalves CA, Kapczinski F. DNA damage in bipolar disorder. Psychiatry Res. 2007;153:27–32.
  • 15. Schulman H. Nitric oxide: a spatial second messenger. Mol Psychiatry. 1997;2:296-9.
  • 16. Papageorgiou C, Grapsa E, Zerefos N, Stamatelopoulos S, Christodoulou GN. Association of serum nitric oxide levels with depressive symptoms: a study with end-stage renal failure patients. Psychother Psychosom. 2001;70: 216–20.
  • 17. Suzuki E, Yagi G, Nakaki T, Kanba S, Asai M. Elevated plasma nitrate levels in depressive states. J Affect Disord. 2001;63:221–4
  • 18. Srivastava N, Barthwal MK, Dalal PK, Agarwal AK, Nag D, Seth PK, et al. A study on nitric oxide, ß- adrenergic receptors and antioxidant status in the polymorphonuclear leukocytes from the patients of depression. J Affect Disord. 2002;72:45–52.
  • 19. Jenkinson CP, Grody WW, Cederbaum SD. Comparative properties of arginases. Comp Biochem Physiol B Biochem Mol Biol. 1996;114:107–32.
  • 20. Albina JE, Mills CD, Henry WL, Caldwell MD. Temporal expression of different pathways of L-arginine metabolism in healing wounds. J Immunol. 1990;144:3877–80.
  • 21. Huang LW, Chang KL, Chen CJ, Liu HW. Arginase levels are increased in patients with rheumatoid arthritis. Kaohsiung J Med Sci. 2001;17:358–63.
  • 22. Durak I, Ozturk HS, Elgun S, Cimen MYB, Yalcyn S. Erythrocyte nitric oxide metabolism in patients with chronic renal failure. Clin Nephrol. 2001;55:460–4.
  • 23. Jansen A, Lewis S, Cattell V, Cook HT. Arginase is a major pathway of L-arginine metabolism in nephritic glomeruli. Kidney Int. 1992;42:1107–12.
  • 24. Szilagyi K. Serum arginase-activity in manic-depressive illness. Arch Psychiatr Nervenkr. 1971;214:390-8.
  • 25. Elgun S, Kumbasar H. Increased serum arginase activity in depressed patients. Prog Neuro Psychopharmacol. Biol Psychiatry. 2000;24:227–32.
  • 26. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th edition. Washington DC: DSMIV-TR; 2004.
  • 27. Akdemir A, Orsel S, Dağ I, Turkçapar H, Iscan N, Ozbay H. Hamilton depresyon derecelendirme ölçeği (HDDÖ)’nin geçerliliği, güvenilirliği ve klinikte kullanımı. 3P Dergisi. 1996;4:251-9.
  • 28. Koltuksuz U, Irmak MK, Karaman A, Uz E, Var A, Ozyurt H, et al. Testicular NO levels after unilateral testicular torsion/detorsion in rats pretreated with caffeinic acid phenethyl ester. Urol Res. 2000;28:360-3.
  • 29. Silberg G, Ben-Shachar D, Navon R. Genetic analysis of nitric oxide synthase 1 variants in schizophrenia and bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2010;5:1318-28.
  • 30. Kowalski J, Labuzek K, Herman ZS. Flupentixol and trifluperidol reduce secretion of tumor necrosis factor-alpha and nitric oxide by rat microglial cells. Neurochem Int. 2003;43:173-8.
  • 31. Wegener G, Volke V, Harvey BH, Rosenberg R. Local, but not systemic, administration of serotonergic antidepressants decreases hippocampal nitric oxide synthase activity. Brain Res. 2003;959:128-34.
There are 30 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Nurdan Özlü Ceylan This is me

İclal Geyikli Çimenci This is me

Ayşe Kılınçaslan This is me

Feridun Bülbül This is me

Haluk A. Savaş This is me

Publication Date January 1, 2011
Published in Issue Year 2011 Volume: 1 Issue: 1

Cite

APA Ceylan, N. Ö., Çimenci, İ. G., Kılınçaslan, A., Bülbül, F., et al. (2011). İki uçlu bozuklukta depresif dönemin tedavisi sırasında plazma nitrik oksit düzeyi ve arginaz aktivitesindeki değişiklikler. Journal of Mood Disorders, 1(1), 1-6.
AMA Ceylan NÖ, Çimenci İG, Kılınçaslan A, Bülbül F, Savaş HA. İki uçlu bozuklukta depresif dönemin tedavisi sırasında plazma nitrik oksit düzeyi ve arginaz aktivitesindeki değişiklikler. Journal of Mood Disorders. January 2011;1(1):1-6.
Chicago Ceylan, Nurdan Özlü, İclal Geyikli Çimenci, Ayşe Kılınçaslan, Feridun Bülbül, and Haluk A. Savaş. “İki uçlu Bozuklukta Depresif dönemin Tedavisi sırasında Plazma Nitrik Oksit düzeyi Ve Arginaz Aktivitesindeki değişiklikler”. Journal of Mood Disorders 1, no. 1 (January 2011): 1-6.
EndNote Ceylan NÖ, Çimenci İG, Kılınçaslan A, Bülbül F, Savaş HA (January 1, 2011) İki uçlu bozuklukta depresif dönemin tedavisi sırasında plazma nitrik oksit düzeyi ve arginaz aktivitesindeki değişiklikler. Journal of Mood Disorders 1 1 1–6.
IEEE N. Ö. Ceylan, İ. G. Çimenci, A. Kılınçaslan, F. Bülbül, and H. A. Savaş, “İki uçlu bozuklukta depresif dönemin tedavisi sırasında plazma nitrik oksit düzeyi ve arginaz aktivitesindeki değişiklikler”, Journal of Mood Disorders, vol. 1, no. 1, pp. 1–6, 2011.
ISNAD Ceylan, Nurdan Özlü et al. “İki uçlu Bozuklukta Depresif dönemin Tedavisi sırasında Plazma Nitrik Oksit düzeyi Ve Arginaz Aktivitesindeki değişiklikler”. Journal of Mood Disorders 1/1 (January 2011), 1-6.
JAMA Ceylan NÖ, Çimenci İG, Kılınçaslan A, Bülbül F, Savaş HA. İki uçlu bozuklukta depresif dönemin tedavisi sırasında plazma nitrik oksit düzeyi ve arginaz aktivitesindeki değişiklikler. Journal of Mood Disorders. 2011;1:1–6.
MLA Ceylan, Nurdan Özlü et al. “İki uçlu Bozuklukta Depresif dönemin Tedavisi sırasında Plazma Nitrik Oksit düzeyi Ve Arginaz Aktivitesindeki değişiklikler”. Journal of Mood Disorders, vol. 1, no. 1, 2011, pp. 1-6.
Vancouver Ceylan NÖ, Çimenci İG, Kılınçaslan A, Bülbül F, Savaş HA. İki uçlu bozuklukta depresif dönemin tedavisi sırasında plazma nitrik oksit düzeyi ve arginaz aktivitesindeki değişiklikler. Journal of Mood Disorders. 2011;1(1):1-6.