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The strong relationship between disease severity and thiol-disulphide homeostasis in patients with restless legs syndrome

Year 2018, Volume: 10 Issue: 4, 436 - 443, 01.12.2018
https://doi.org/10.21601/ortadogutipdergisi.475395

Abstract

Objective: This study was conducted to investigate thiol-disulphide homeostasis, a novel oxidative stress marker in primary restless legs syndrome (RLS) patients.

Material and Method: Thirty-eight patients and 43 healthy subjects were included in the study. Serum native thiol, total thiol, disulphide and disulphide / native thiol percent ratio levels were measured by using a novel automated method. Diagnosis of RLS was based on the criteria proposed by the International Restless Legs Syndrome Study Group (IRLSSG), and RLS severity was assessed using the IRLSSG Severity Scale.

Results: Serum native thiol and total thiol levels were significantly lower (p< 0.001; p= 0.007, respectively) while disulphide and disulphide/native thiol percent ratio levels significantly higher (p= 0.017; p< 0.001, respectively), in patients with RLS compared with control group. Significant correlations were found between the IRLSSG Severity Scale and thiol-disulphide homeostasis parameters (r= -0.56, p< 0.001 for native thiol; r= -0.51, p< 0.001 for total thiol; r= 0.37, p= 0.020 for disulphide and r= 0.60, p< 0.001 for disulphide/native thiol percent ratio).







Conclusions: Decreased native thiol, increased disulphide levels and increased disulphide/native thiol percent ratio show that thiol-disulphide balance shifted to the oxidation side. Strong correlations between the IRLSSG Severity Scale and thiol-disulphide homeostasis parameters indicate that homeostasis may have a role in the pathogenesis of the Primary RLS.

References

  • 1. Koo, B.B., K. Bagai, and A.S. Walters, Restless legs syndrome: current concepts about disease pathophysiology. Tremor and Other Hyperkinetic Movements, 2016. 6.
  • 2. Kim, J. and A.G. Hartzema, Adherence and persistence to ropinirole, pramipexole, and gabapentin in patients with newly diagnosed restless legs syndrome. Sleep medicine, 2018. 44: p. 45-52.
  • 3. Akpinar, S., Restless legs syndrome treatment with dopaminergic drugs. Clinical neuropharmacology, 1987. 10(1): p. 69-79.
  • 4. Iranzo, A., C.L. Comella, J. Santamaria, and W. Oertel, Restless legs syndrome in Parkinson's disease and other neurodegenerative diseases of the central nervous system. Movement disorders: official journal of the Movement Disorder Society, 2007. 22(S18): p. S424-S430.
  • 5. Mitchell, U.H., J.D. Obray, E. Hunsaker, B.T. Garcia, T.J. Clarke, S. Hope, et al., Peripheral Dopamine in restless legs syndrome. Frontiers in neurology, 2018. 9: p. 155.
  • 6. Baskol, G., S. Korkmaz, F. Erdem, A. Caniklioglu, M. Kocyigit, and M. Aksu, Assessment of nitric oxide, advanced oxidation protein products, malondialdehyde, and thiol levels in patients with restless legs syndrome. Sleep medicine, 2012. 13(4): p. 414-418.
  • 7. Erel, O. and S. Neselioglu, A novel and automated assay for thiol/disulphide homeostasis. Clinical biochemistry, 2014. 47(18): p. 326-332.
  • 8. Gumusyayla, S., G. Vural, H. Bektas, O. Deniz, S. Neselioglu, and O. Erel, A novel oxidative stress marker in patients with Alzheimer’s disease: dynamic thiol–disulphide homeostasis. Acta neuropsychiatrica, 2016. 28(6): p. 315-320.
  • 9. Vural, G., S. Gumusyayla, H. Bektas, O. Deniz, M. Alisik, and O. Erel, Impairment of dynamic thiol–disulphide homeostasis in patients with idiopathic Parkinson’s disease and its relationship with clinical stage of disease. Clinical neurology and neurosurgery, 2017. 153: p. 50-55.
  • 11. Gumusyayla, S., G. Vural, H. Bektas, S. Neselioglu, O. Deniz, and O. Erel, A novel oxidative stress marker in migraine patients: dynamic thiol–disulphide homeostasis. Neurological Sciences, 2016. 37(8): p. 1311-1317.
  • 11. Kundi, H., M. Gok, M. Cetin, E. Kiziltunç, C. Topcuoglu, S. Neşelioğlu, et al., Association of thiol disulfide homeostasis with slow coronary flow. Scandinavian Cardiovascular Journal, 2016. 50(4): p. 213-217.
  • 12. Altiparmak, I.H., M.E. Erkus, H. Sezen, R. Demirbag, Z. Kaya, Y. Sezen, et al., Evaluation of thiol levels, thiol/disulfide homeostasis and their relation with inflammation in cardiac syndrome X. Coronary artery disease, 2016. 27(4): p. 295-301.
  • 13. Babaoglu, E., H. Kilic, H. Hezer, O. Dag, E. Parlak, A. Senturk, et al., Comparison of thiol/disulphide homeostasis parameters in patients with COPD, asthma and ACOS. Eur Rev Med Pharmacol Sci, 2016. 20(8): p. 1537-1543.
  • 14. Allen, R.P., D.L. Picchietti, D. Garcia-Borreguero, W.G. Ondo, A.S. Walters, J.W. Winkelman, et al., Restless legs syndrome/Willis–Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria–history, rationale, description, and significance. Sleep medicine, 2014. 15(8): p. 860-873.
  • 15. Erden, İ., E.Ç. Erden, H. Durmuş, H. Tıbıllı, M. Tabakçı, M.E. Kalkan, et al., Association between restless leg syndrome and slow coronary flow. Anatol J Cardiol, 2014. 14: p. 612-6.
  • 16. Higuchi, T., M. Abe, M. Mizuno, T. Yamazaki, H. Suzuki, M. Moriuchi, et al., Association of restless legs syndrome with oxidative stress and inflammation in patients undergoing hemodialysis. Sleep Med, 2015. 16(8): p. 941-8.
  • 17. Cikrikcioglu, M.A., M. Hursitoglu, H. Erkal, B.E. Kinas, J. Sztajzel, M. Cakirca, et al., Oxidative stress and autonomic nervous system functions in restless legs syndrome. Eur J Clin Invest, 2011. 41(7): p. 734-42.
  • 18. Altıparmak, I.H., M.E. Erkuş, H. Sezen, R. Demirbag, O. Gunebakmaz, Z. Kaya, et al., The relation of serum thiol levels and thiol/disulphide homeostasis with the severity of coronary artery disease. Kardiologia Polska (Polish Heart Journal), 2016. 74(11): p. 1346-1353.
  • 19. Unal, K., G. Erzin, R.N. Yuksel, M. Alisik, and O. Erel, Thiol/disulphide homeostasis in schizophrenia patients with positive symptoms. Nord J Psychiatry, 2018. 72(4): p. 281-284.
  • 20. Turell, L., R. Radi, and B. Alvarez, The thiol pool in human plasma: the central contribution of albumin to redox processes. Free Radic Biol Med, 2013. 65: p. 244-53.21. Ergin, M., B.D. Cendek, S. Neselioglu, A.F. Avsar, and O. Erel, Dynamic thiol-disulfide homeostasis in hyperemesis gravidarum. J Perinatol, 2015. 35(10): p. 788-92.
  • 22. Allen, R.P., D.L. Picchietti, M. Auerbach, Y.W. Cho, J.R. Connor, C.J. Earley, et al., Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis-Ekbom disease in adults and children: an IRLSSG task force report. Sleep medicine, 2018. 41: p. 27-44.
  • 23. Sabens, E.A., A.M. Distler, and J.J. Mieyal, Levodopa deactivates enzymes that regulate thiol-disulfide homeostasis and promotes neuronal cell death: implications for therapy of Parkinson's disease. Biochemistry, 2010. 49(12): p. 2715-24.
  • 24. Ma, L.Y., N. Camerman, J.K. Swartzendruber, N.D. Jones, and A. Camerman, Stereochemistry of dopaminergic ergoline derivatives: structures of pergolide and pergolide mesylate. Canadian journal of chemistry, 1987. 65(2): p. 256-260.
  • 25. Bennett Jr, J.P. and M.F. Piercey, Pramipexole—a new dopamine agonist for the treatment of Parkinson's disease. Journal of the neurological sciences, 1999. 163(1): p. 25-31.
  • 26. Kehr, J., X.-J. Hu, T. Yoshitake, and D. Scheller, Determination of the dopamine agonist rotigotine in microdialysates from the rat brain by microbore column liquid chromatography with electrochemical detection. Journal of Chromatography B, 2007. 845(1): p. 109-113.
  • 27. Chasteen, N.D., The identification of the probable locus of iron and anion binding in the transferrins. Trends in Biochemical Sciences, 1983. 8(8): p. 272-275.
  • 28. Harrison, P.M., The structure and function of ferritin. Biochemical education, 1986. 14(4): p. 154-162.
  • 29. Malorni, W., U. Testa, G. Rainaldi, E. Tritarelli, and C. Peschle, Oxidative stress leads to a rapid alteration of transferrin receptor intravesicular trafficking. Experimental cell research, 1998. 241(1): p. 102-116.
  • 30. Johnson, D.C., D.R. Dean, A.D. Smith, and M.K. Johnson, Structure, function, and formation of biological iron-sulfur clusters. Annu Rev Biochem, 2005. 74: p. 247-81.

Huzursuz bacak sendromlu hastalarda hastalık şiddeti ve tiyol-disülfid homeostazı arasındaki güçlü ilişki

Year 2018, Volume: 10 Issue: 4, 436 - 443, 01.12.2018
https://doi.org/10.21601/ortadogutipdergisi.475395

Abstract

Amaç:
Bu çalışma, primer huzursuz bacak sendromu (RLS) hastalarında yeni bir
oksidatif stres belirteci olan tiyol-disülfid homeostazisini araştırmak
amacıyla yapıldı.

Gereç
ve Yöntem:
Otuz sekiz hasta ve 43 sağlıklı birey çalışmaya
alındı. Serum nativ tiyol, total tiyol, disülfit ve disülfid / nativ tiyol
oranları yeni bir otomatik yöntem kullanılarak ölçülmüştür. RLS tanısı
Uluslararası Huzursuz Bacak Sendromu Çalışma Grubu (IRLSSG) tarafından önerilen
kriterlere gore konuldu ve RLS şiddeti IRLSSG Şiddet Ölçeği kullanılarak
değerlendirildi.

Bulgular:
Serum nativ tiyol ve total tiyol düzeyleri anlamlı derecede düşük (sırasıyla
p<0.001; p=0.007), disülfid ve disülfid / nativ tiyol oranı anlamlı olarak
daha yüksekti (sırasıyla p=0.017; p<0.001). RLS kontrol grubu ile
karşılaştırıldı. IRLSSG Önem Ölçeği ve tiyol-disülfid homeostasisi
parametreleri arasında anlamlı korelasyonlar bulundu (r=-0.56, nativ tiyol için
p<0.001; total tiyol için r=-0.51, p<0.001; disülfid için r=0.37, p=0.020);
r=0.60, disülfid / nativ tiyol yüzdesi oranı için p<0.001).







Sonuçlar:
Azalmış nativ tiyol, artan disülfid seviyeleri ve artmış disülfid / nativ tiyol
oranı, tiyol-disülfür dengesinin oksidasyon tarafına kaydığını göstermektedir.
IRLSSG Önem Ölçeği ve tiyol-disülfid homeostasisi parametreleri arasındaki
güçlü korelasyonlar, homeostazın primer RLS'nin patogenezinde rol
oynayabileceğini göstermektedir.

References

  • 1. Koo, B.B., K. Bagai, and A.S. Walters, Restless legs syndrome: current concepts about disease pathophysiology. Tremor and Other Hyperkinetic Movements, 2016. 6.
  • 2. Kim, J. and A.G. Hartzema, Adherence and persistence to ropinirole, pramipexole, and gabapentin in patients with newly diagnosed restless legs syndrome. Sleep medicine, 2018. 44: p. 45-52.
  • 3. Akpinar, S., Restless legs syndrome treatment with dopaminergic drugs. Clinical neuropharmacology, 1987. 10(1): p. 69-79.
  • 4. Iranzo, A., C.L. Comella, J. Santamaria, and W. Oertel, Restless legs syndrome in Parkinson's disease and other neurodegenerative diseases of the central nervous system. Movement disorders: official journal of the Movement Disorder Society, 2007. 22(S18): p. S424-S430.
  • 5. Mitchell, U.H., J.D. Obray, E. Hunsaker, B.T. Garcia, T.J. Clarke, S. Hope, et al., Peripheral Dopamine in restless legs syndrome. Frontiers in neurology, 2018. 9: p. 155.
  • 6. Baskol, G., S. Korkmaz, F. Erdem, A. Caniklioglu, M. Kocyigit, and M. Aksu, Assessment of nitric oxide, advanced oxidation protein products, malondialdehyde, and thiol levels in patients with restless legs syndrome. Sleep medicine, 2012. 13(4): p. 414-418.
  • 7. Erel, O. and S. Neselioglu, A novel and automated assay for thiol/disulphide homeostasis. Clinical biochemistry, 2014. 47(18): p. 326-332.
  • 8. Gumusyayla, S., G. Vural, H. Bektas, O. Deniz, S. Neselioglu, and O. Erel, A novel oxidative stress marker in patients with Alzheimer’s disease: dynamic thiol–disulphide homeostasis. Acta neuropsychiatrica, 2016. 28(6): p. 315-320.
  • 9. Vural, G., S. Gumusyayla, H. Bektas, O. Deniz, M. Alisik, and O. Erel, Impairment of dynamic thiol–disulphide homeostasis in patients with idiopathic Parkinson’s disease and its relationship with clinical stage of disease. Clinical neurology and neurosurgery, 2017. 153: p. 50-55.
  • 11. Gumusyayla, S., G. Vural, H. Bektas, S. Neselioglu, O. Deniz, and O. Erel, A novel oxidative stress marker in migraine patients: dynamic thiol–disulphide homeostasis. Neurological Sciences, 2016. 37(8): p. 1311-1317.
  • 11. Kundi, H., M. Gok, M. Cetin, E. Kiziltunç, C. Topcuoglu, S. Neşelioğlu, et al., Association of thiol disulfide homeostasis with slow coronary flow. Scandinavian Cardiovascular Journal, 2016. 50(4): p. 213-217.
  • 12. Altiparmak, I.H., M.E. Erkus, H. Sezen, R. Demirbag, Z. Kaya, Y. Sezen, et al., Evaluation of thiol levels, thiol/disulfide homeostasis and their relation with inflammation in cardiac syndrome X. Coronary artery disease, 2016. 27(4): p. 295-301.
  • 13. Babaoglu, E., H. Kilic, H. Hezer, O. Dag, E. Parlak, A. Senturk, et al., Comparison of thiol/disulphide homeostasis parameters in patients with COPD, asthma and ACOS. Eur Rev Med Pharmacol Sci, 2016. 20(8): p. 1537-1543.
  • 14. Allen, R.P., D.L. Picchietti, D. Garcia-Borreguero, W.G. Ondo, A.S. Walters, J.W. Winkelman, et al., Restless legs syndrome/Willis–Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria–history, rationale, description, and significance. Sleep medicine, 2014. 15(8): p. 860-873.
  • 15. Erden, İ., E.Ç. Erden, H. Durmuş, H. Tıbıllı, M. Tabakçı, M.E. Kalkan, et al., Association between restless leg syndrome and slow coronary flow. Anatol J Cardiol, 2014. 14: p. 612-6.
  • 16. Higuchi, T., M. Abe, M. Mizuno, T. Yamazaki, H. Suzuki, M. Moriuchi, et al., Association of restless legs syndrome with oxidative stress and inflammation in patients undergoing hemodialysis. Sleep Med, 2015. 16(8): p. 941-8.
  • 17. Cikrikcioglu, M.A., M. Hursitoglu, H. Erkal, B.E. Kinas, J. Sztajzel, M. Cakirca, et al., Oxidative stress and autonomic nervous system functions in restless legs syndrome. Eur J Clin Invest, 2011. 41(7): p. 734-42.
  • 18. Altıparmak, I.H., M.E. Erkuş, H. Sezen, R. Demirbag, O. Gunebakmaz, Z. Kaya, et al., The relation of serum thiol levels and thiol/disulphide homeostasis with the severity of coronary artery disease. Kardiologia Polska (Polish Heart Journal), 2016. 74(11): p. 1346-1353.
  • 19. Unal, K., G. Erzin, R.N. Yuksel, M. Alisik, and O. Erel, Thiol/disulphide homeostasis in schizophrenia patients with positive symptoms. Nord J Psychiatry, 2018. 72(4): p. 281-284.
  • 20. Turell, L., R. Radi, and B. Alvarez, The thiol pool in human plasma: the central contribution of albumin to redox processes. Free Radic Biol Med, 2013. 65: p. 244-53.21. Ergin, M., B.D. Cendek, S. Neselioglu, A.F. Avsar, and O. Erel, Dynamic thiol-disulfide homeostasis in hyperemesis gravidarum. J Perinatol, 2015. 35(10): p. 788-92.
  • 22. Allen, R.P., D.L. Picchietti, M. Auerbach, Y.W. Cho, J.R. Connor, C.J. Earley, et al., Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis-Ekbom disease in adults and children: an IRLSSG task force report. Sleep medicine, 2018. 41: p. 27-44.
  • 23. Sabens, E.A., A.M. Distler, and J.J. Mieyal, Levodopa deactivates enzymes that regulate thiol-disulfide homeostasis and promotes neuronal cell death: implications for therapy of Parkinson's disease. Biochemistry, 2010. 49(12): p. 2715-24.
  • 24. Ma, L.Y., N. Camerman, J.K. Swartzendruber, N.D. Jones, and A. Camerman, Stereochemistry of dopaminergic ergoline derivatives: structures of pergolide and pergolide mesylate. Canadian journal of chemistry, 1987. 65(2): p. 256-260.
  • 25. Bennett Jr, J.P. and M.F. Piercey, Pramipexole—a new dopamine agonist for the treatment of Parkinson's disease. Journal of the neurological sciences, 1999. 163(1): p. 25-31.
  • 26. Kehr, J., X.-J. Hu, T. Yoshitake, and D. Scheller, Determination of the dopamine agonist rotigotine in microdialysates from the rat brain by microbore column liquid chromatography with electrochemical detection. Journal of Chromatography B, 2007. 845(1): p. 109-113.
  • 27. Chasteen, N.D., The identification of the probable locus of iron and anion binding in the transferrins. Trends in Biochemical Sciences, 1983. 8(8): p. 272-275.
  • 28. Harrison, P.M., The structure and function of ferritin. Biochemical education, 1986. 14(4): p. 154-162.
  • 29. Malorni, W., U. Testa, G. Rainaldi, E. Tritarelli, and C. Peschle, Oxidative stress leads to a rapid alteration of transferrin receptor intravesicular trafficking. Experimental cell research, 1998. 241(1): p. 102-116.
  • 30. Johnson, D.C., D.R. Dean, A.D. Smith, and M.K. Johnson, Structure, function, and formation of biological iron-sulfur clusters. Annu Rev Biochem, 2005. 74: p. 247-81.
There are 29 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Original article
Authors

Salim Neşelioğlu 0000-0002-0974-5717

Yasemin Eren This is me

Ebru Bilge Dirik This is me

Emine Feyza Yurt This is me

Serpil Erdogan

Orhan Deniz This is me

Özcan Erel

Publication Date December 1, 2018
Published in Issue Year 2018 Volume: 10 Issue: 4

Cite

Vancouver Neşelioğlu S, Eren Y, Dirik EB, Yurt EF, Erdogan S, Deniz O, Erel Ö. The strong relationship between disease severity and thiol-disulphide homeostasis in patients with restless legs syndrome. otd. 2018;10(4):436-43.

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