Polisitemi Veralı Hastalarda Dinamik Thiol/Disulfit Dengesi ve İskemi Modifiye Albumin Düzeyleri

Year 2021, Volume: 23 Issue: 2, 137 - 141, 30.08.2021

Mahmut Bakır Koyuncu , Hakan Basir Mustafa Ilgan Mehmet Ali Uçar , Aydan Akdeniz , Anıl Tombak , Eyüp Naci Tiftik , Salim Neşelioğlu , Özcan Erel

https://doi.org/10.18678/dtfd.890142

Abstract

Amaç: Polisitemi vera, eritrosit artışı ve JAK2 mutasyonu pozitifliği ile karakterize olan kronik bir miyeloproliferatif hastalıktır. Polisitemi veralı hastalarda miyelofibroz ve akut lösemiye dönüşüm görülebilir. Oksidatif stres, DNA hasarına neden olur ve malign dönüşüme yol açabilir. Tiyol molekülleri, oksidatif stresin zararlı etkilerini önleyebilir. Bu nedenle, bu çalışmada polisitemi veralı hastalarda tiyol homeostazı durumunun analiz edilmesi amaçlandı.
Gereç ve Yöntemler: Bu çalışmaya polisitemi veralı 31 hasta ve 80 sağlıklı gönüllü dahil edildi. Vakaların serum örnekleri toplanarak çalışma sonuna kadar saklandı. Doğal tiyol, toplam tiyol, disülfit ve iskemi modifiye albümin seviyeleri belirlendi.
Bulgular: Ortalama iskemi modifiye albümin (1,09±0,21'e karşı 0,67±0,08; p<0,001), ortalama disülfit (23,5±6,1'e karşı 10,7±2,6; p<0,001), ortalama disülfit/doğal tiyol oranı (5,6±1,1'e karşı 3,1±1,2; p<0,001), ortalama disülfit/toplam tiyol oranı (5,0±0,9'a karşı 2,9±1,0; p<0,001), ortalama doğal tiyol (418,9±80,6'ya karşı 371,4±103,7; p=0,024), ortalama toplam tiyol (466,0±89,8 393,0±105,5; p=0,001) ve ortalama disülfit/toplam tiyol oranı (89,8±1,8'e karşı 94,1±2,0; p<0,001) polisitemi vera hastalarında daha yüksek idi. İskemi modifiye albümin düzeyleri ayrıca yüksek riskli polisitemi vera hastalarında daha yüksek idi. Ruksolitinib tedavisi alan hastalar daha yüksek doğal tiyol, toplam tiyol ve disülfit seviyeleri ile daha yüksek disülfit/doğal tiyol ve disülfit/toplam tiyol oranlarına sahipti.
Sonuç: Tedavi altında olan polisitemi veralı hastalarda oksidatif stres belirteçleri hala yüksektir. Ayrıca, ruxolitinib bu hastalarda oksidatif stresi azaltmak için faydalı olabilir.

Keywords

disulfit, polistemi vera, oksidatif stres, tiyol

Dynamic Thiol/Disulfide Balance and Ischemia Modified Albumin Levels in Patients with Polycythemia Vera

Abstract

Aim: Polycythemia vera is a chronic myeloproliferative disease characterized by increased red cell mass and JAK2 mutation positivity. Transformation to myelofibrosis and acute leukemia is possible in patients with polycythemia vera. Oxidative stress causes DNA damage and might be a reason for malignant transformation. Thiol molecules can prevent the harmful effects of oxidative stress. Therefore, in this study, we aimed to analyze the state of thiol homeostasis in patients with polycythemia vera.
Material and Methods: Thirty-one patients with polycythemia vera and 80 healthy volunteers were included in this study. Serum samples of the cases were stored until the end of the study. Native thiol, total thiol, disulfide, and ischemia modified albumin levels were determined.
Results: The mean ischemia modified albumin (1.09±0.21 vs 0.67±0.08; p<0.001, mean disulfide (23.5±6.1 vs 10.7±2.6; p<0.001), the mean disulfide/native thiol ratio (5.6±1.1 vs 3.1±1.2; p<0.001), the mean disulfide/total thiol ratio (5.0±0.9 vs 2.9±1.0; p<0.001), the mean native thiol (418.9±80.6 vs 371.4±103.7; p=0.024), the mean total thiol (466.0±89.8 vs 393.0±105.5; p=0.001) and the mean disulfide/total thiol ratio (89.8±1.8 vs 94.1±2.0; p<0.001) were found higher in polycythemia vera patients. Ischemia modified albumin levels were also higher in high-risk polycythemia vera patients. Patients on ruxolitinib therapy had higher native thiol, total thiol and disulfide levels, and higher disulfide/native thiol and disulfide/total thiol ratios.
Conclusion: Oxidative stress markers are still high in patients with polycythemia vera who were under treatment. Besides, ruxolitinib may be helpful to decrease oxidative stress in these patients.

Keywords

disulfide, polycythemia vera, oxidative stress, thiol

References

• Büyükaşik Y, Alİ R, Ar C, Turgut M, Yavuz S, Saydam G. Polycythemia vera: diagnosis, clinical course, and current management. Turk J Med Sci. 2018;48(4):698-710.
• Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol. 2009;7(1):65-74.
• Winterbourn CC, Hampton MB. Thiol chemistry and specificity in redox signaling. Free Radic Biol Med. 2008;45(5):549-61.
• Ucar MA, Tombak A, Dagdas S, Akdeniz A, Ceran F, Neselioglu S, et al. Is dynamic thiol/disulfide homeostasis associated with the prognosis of myelodysplastic syndrome? J Med Biochem. 2020;39(3):336-45.
• Kundi H, Ates I, Kiziltunc E, Cetin M, Cicekcioglu H, Neselioglu S, et al. A novel oxidative stress marker in acute myocardial infarction; thiol/disulphide homeostasis. Am J Emerg Med. 2015;33(11):1567-71.
• Demirseren DD, Cicek C, Alisik M, Demirseren ME, Aktaş A, Erel O. Dynamic thiol/disulphide homeostasis in patients with basal cell carcinoma. Cutan Ocul Toxicol. 2017;36(3):278-82.
• Eryilmaz MA, Kozanhan B, Solak I, Çetinkaya ÇD, Neselioglu S, Erel Ö. Thiol-disulfide homeostasis in breast cancer patients. J Cancer Res Ther. 2019;15(5):1062-6.
• Dirican N, Dirican A, Sen O, Aynali A, Atalay S, Bircan HA, et al. Thiol/disulfide homeostasis: A prognostic biomarker for patients with advanced non-small cell lung cancer? Redox Rep. 2016;21(5):197-203.
• Gündüztepe Y, Bukan N, Zorlu E, Karaman Y, Andaç Topkan T, Gurbuz N, et al. The evaluation of thiol-disulfıte balance, ischemıa albumın modıfıcation and seruloplazmine as a new oxidatıve stress in mild cognitive impairment and early stage alzheimer's disease patients. J Clin Neurosci. 2020;75:188-94.
• Gulpamuk B, Tekin K, Sonmez K, Inanc M, Neselioglu S, Erel O, et al. The significance of thiol/disulfide homeostasis and ischemia-modified albumin levels to assess the oxidative stress in patients with different stages of diabetes mellitus. Scand J Clin Lab Invest. 2018;78(1-2):136-42.
• Bar-Or D, Lau E, Winkler JV. A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia-a preliminary report. J Emerg Med. 2000;19(4):311-5.
• Karaşin SS, Çift T. The role of ischemia-modified albumin as a biomarker in preeclampsia. Rev Bras Ginecol Obstet. 2020;42(3):133-9.
• Oran I, Oran B. Ischemia-modified albumin as a marker of acute coronary syndrome: the case for revising the concept of "N-terminal modification" to "Fatty Acid Occupation" of albumin. Dis Markers. 2017;2017:5692583.
• Sahin A, Turkoglu S, Tunc N, Duzenci D, Solmaz OA, Bahcecioglu IH, et al. Is ischemia-modified albumin a reliable tool for the assessment of acute pancreatitis? Ther Clin Risk Manag. 2018;14:627-35.
• Finazzi G, Barbui T. How I treat patients with polycythemia vera. Blood. 2007;109(12):5104-11.
• Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem. 2014;47(18):326-32.
• Pascu VÎnturiȘ EG, GĂman AM. Assessment of oxidative stress in patients with chronic myeloid leukemia depending on associated comorbidities. Curr Health Sci J. 2020;46(1):23-30.
• Rossi C, Zini R, Rontauroli S, Ruberti S, Prudente Z, Barbieri G, et al. Role of TGF-β1/miR-382-5p/SOD2 axis in the induction of oxidative stress in CD34+ cells from primary myelofibrosis. Mol Oncol. 2018;12(12):2102-23.
• Bjørn ME, Hasselbalch HC. The role of reactive oxygen species in myelofibrosis and related neoplasms. Mediators Inflamm. 2015;2015:648090.
• Allegra A, Pioggia G, Tonacci A, Casciaro M, Musolino C, Gangemi S. Synergic crosstalk between inflammation, oxidative stress, and genomic alterations in BCR-ABL-negative myeloproliferative neoplasm. Antioxidants (Basel). 2020;9(11):1037.
• Musolino C, Allegra A, Saija A, Alonci A, Russo S, Spatari G, et al. Changes in advanced oxidation protein products, advanced glycation end products, and s-nitrosylated proteins, in patients affected by polycythemia vera and essential thrombocythemia. Clin Biochem. 2012;45(16-17):1439-43.
• Durmus A, Mentese A, Yilmaz M, Sumer A, Akalin I, Topal C, et al. The thrombotic events in polycythemia vera patients may be related to increased oxidative stress. Med Princ Pract. 2014;23(3):253-8.
• Pilo F, Angelucci E. A storm in the niche: Iron, oxidative stress and haemopoiesis. Blood Rev. 2018;32(1):29-35.
• Winterbourn CC. Are free radicals involved in thiol-based redox signaling? Free Radic Biol Med. 2015;80:164-70.
• Poole LB. The basics of thiols and cysteines in redox biology and chemistry. Free Radic Biol Med. 2015;80:148-57.
• Ellidag HY, Aydin O, Eren E, Yilmaz N, Ergin M. Decreased HDL-dependent paraoxonase and arylesterase enzyme activity may indicate a worse prognosis in multiple myeloma. Asian Pac J Cancer Prev. 2014;15(22):9847-51.