THIOL-DISULFIDE HOMEOSTASIS IN MYASTHENIA GRAVIS
Yıl 2025,
Cilt: 15 Sayı: 3, 324 - 330, 15.09.2025
Mariam Kavakcı
,
Merve Okuyucu
,
Salim Neşelioğlu
,
Evren Yaşar
,
Özcan Erel
Öz
Objective: Neuromuscular junction disorders (NJD), characterized by a dysfunction in neuromuscular transmission, may be associated with oxidative stress. This study aimed to evaluate the role of thiol-disulfide homeostasis as an index of oxidative stress in adult patients with NJD (i.e., myasthenia gravis) compared to healthy controls, considering its potential as a biomarker and therapeutic target.
Materials and Methods: This study included 46 patients with myasthenia gravis and 46 age- and gender-matched healthy controls. Blood samples were collected and analyzed for thiol-disulfide homeostasis parameters, total antioxidant status (TAS), and ischemia-modified albumin (IMA) using spectrophotometric and colorimetric methods. Statistical analysis was conducted using SPSS to compare the groups and examine correlations between oxidative and antioxidant markers.
Results: Patients showed significantly lower levels of native thiol, total thiol, and TAS, and higher levels of disulfide, disulfide/native thiol percentage ratio, and IMA compared to controls (p<0.05 for all). These findings indicate increased oxidative stress and disrupted antioxidant defense in patients with myasthenia gravis. There were also significant correlations between decreased antioxidant parameters and increased oxidative stress markers.
Conclusion: This study confirms that thiol-disulfide homeostasis is significantly altered in patients with myasthenia gravis, highlighting its potential role as a biomarker for disease pathogenesis and a target for therapeutic intervention. Future research could expand on these findings to develop targeted therapies aimed at restoring redox balance in patients with NJD.
Etik Beyan
This study was approved by the ethics committee of Ankara Bilkent City Hospital (Approval Code: E2-23-4412).
Kaynakça
-
1. Punga AR, Maddison P, Heckmann JM, Guptill JT, Evoli A.
Epidemiology, diagnostics, and biomarkers of autoimmune
neuromuscular junction disorders. Lancet Neurol 2022; 21(2):176-
88.
-
2. Mercuri E, Bönnemann CG, Muntoni F. Muscular dystrophies.
Lancet 2019; 394(10213):2025-38.
-
3. Verma S, Khurana S, Vats A, Sahu B, Ganguly NK, Chakraborti P,
et al. Neuromuscular junction dysfunction in amyotrophic lateral
sclerosis. Mol Neurobiol 2022; 59(3):1502-27.
-
4. Hehir MK, Silvestri NJ. Generalized myasthenia gravis: classification,
clinical presentation, natural history, and epidemiology. Neurol Clin.
2018; 36(2):253-60.
-
5. Tannemaat MR, Huijbers MG, Verschuuren JJGM. Myasthenia
gravis-pathophysiology, diagnosis, and treatment. Handb Clin
Neurol. 2024; 200:283-305.
-
6. Panpallı Ateş M. Clinical features of myasthenia gravis patients’:
The assessment of 138 patients. J Contemp Med. September 2021;
11(5):694-8.
-
7. Tekeşin A, Şişman Ç, Toprak UE, Sar A, Akalin B, Koşargelir G, et
al. Evaluation of nonmotor symptoms in myasthenia gravis patients.
Turk J Med Sci. 2024; 55(1):127-39.
-
8. Öncel S, Tunç A. Unveiling myasthenia gravis: A comprehensive
analysis of diagnostic tools and clinical insights. diclemedj. 2023;
50(4):482-9.
-
9. Aydın S, Kethüdaoğlu MO, Göçen HB, Albayrak HE, Köseoğlu A,
Altunok MK, et al. Effects of treatments applied in myasthenia gravis
on gait: Review. IGUSABDER. 2024; 459–67.
-
10. Dobrowolny G, Barbiera A, Sica G, Scicchitano BM. Age-related
alterations at neuromuscular junction: role of oxidative stress and
epigenetic modifications. Cells. 2021; 10(6):1307.
-
11. Jomova K, Raptova R, Alomar SY, Alwasel SH, Nepovimova E,
Kuca K, et al. Reactive oxygen species, toxicity, oxidative stress,
and antioxidants: chronic diseases and aging. Arch of Toxicol 2023;
97(10):2499-574.
-
12. Ionescu-Tucker A, Cotman CW. Emerging roles of oxidative
stress in brain aging and Alzheimer's disease. Neurobiol Aging 2021;
107:86-95.
-
13. Spaas J, van Veggel L, Schepers M, Tiane A, van Horssen J,
Wilson DM 3rd, et al. Oxidative stress and impaired oligodendrocyte
precursor cell differentiation in neurological disorders. Cell Mol Life
Sci 2021; 78(10):4615-37.
-
14. Teleanu DM, Niculescu AG, Lungu II, Radu CI, Vladâcenco O, Roza
E, et al. An overview of oxidative stress, neuroinflammation, and
neurodegenerative diseases. Int J Mol Sci 2022;25;23(11):5938.
-
15. Hajam YA, Rani R, Ganie SY, Sheikh TA, Javaid D, Qadri SS, et
al. Oxidative stress in human pathology and aging: Molecular
mechanisms and perspectives. Cells 2022;5;11(3):552.
-
16. González-Jamett A, Vásquez W, Cifuentes-Riveros G, MartínezPando R, Sáez JC, Cárdenas AM. Oxidative Stress, Inflammation and
Connexin Hemichannels in Muscular Dystrophies. Biomedicines.
2022;21;10(2):507.
-
17. Erel Ö, Erdoğan S. Thiol-disulfide homeostasis: an integrated
approach with biochemical and clinical aspects. Turk J Med Sci 2020;
50(SI-2):1728-38.
-
18. Ergin M, Aydin C, Yurt EF, Cakir B, Erel O. The variation of disulfides
in the progression of type 2 diabetes mellitus. Exp Clin Endocrinol
Diabetes 2020; 128(2):77-81.
-
19. Erzin G, Özkaya G, Topçuoğlu C, Yüksel RN, Erel, Ö, Yurt EF, et al.
Thiol/disulfide homeostasis in bipolar and unipolar depression. Clin
Psychopharmacol Neurosci 2020; 18(3):395-401.
-
20. Caliskan HM, Sivri S, Sokmen E, Celik M, Ilanbey B, Ozbek SC,
et al. Prognostic value of thiol/disulfide homeostasis in symptomatic
patients with heart failure. Arch Physiol Biochem 2021; 127(5):462-
7.
-
21. Güngör İ, Erdem AB, Kavaklı HŞ, Kösem A, Erel Ö, Neşelioğlu S.
Evaluation of thiol-disulfide homeostasis and ischemia-modified
albumin levels in patients presenting to the emergency department
in the postictal period. Turk Noroloji Derg. 2023; 29(2):118–25.
-
22. Sezgin B, Kinci MF, Pirinççi F, Camuzcuoğlu A, Erel Ö, Neşelioğlu S,
et al. Thiol-disulfide status of patients with cervical cancer. J Obstet
Gynaecol Res 2020; 46(11):2423-9.
-
23. Şener MU, Sönmez Ö, Keyf İA, Erel Ö, Alışık M, Bulut S, et al.
Evaluation of thiol/disulfide homeostasis in lung cancer. Turk Thorac
J 2020; 21(4):255-60.
-
24. 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.
-
25. Erel O, Neselioglu S. A novel and automated assay for thiol/
disulphide homeostasis. Clin Biochem 2014; 47(18):326-32.
-
26. Erel O. A novel automated direct measurement method for
total antioxidant capacity using a new generation, more stable ABTS
radical cation. Clin Biochem 2004; 37(4):277-85.
-
27. 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.
-
28. Alqahtani T, Deore SL, Kide AA, Shende BA, Sharma R, Dadarao
Chakole R, et al. Mitochondrial dysfunction and oxidative stress
in Alzheimer's disease, and Parkinson's disease, Huntington's
disease and Amyotrophic Lateral Sclerosis -An updated review.
Mitochondrion 2023; 71:83-92.
-
29. Cunha-Oliveira T, Montezinho L, Mendes C, Firuzi O, Saso
L, Oliveira PJ, et al. Oxidative Stress in Amyotrophic Lateral
Sclerosis: Pathophysiology and Opportunities for Pharmacological
Intervention. Oxid Med Cell Longev. 2020;2020:5021694.
-
30. Melms A, Schalke BC, Kirchner T, Müller-Hermelink HK, Albert E,
Wekerle H. Thymus in myasthenia gravis. Isolation of T-lymphocyte
lines specific for the nicotinic acetylcholine receptor from thymuses
of myasthenic patients. J Clin Invest 1988; 81(3):902-8.
-
31. Marcovecchio GE, Ferrua F, Fontana E, Beretta S, Genua M,
Bortolomai I, et al. Premature Senescence and Increased Oxidative
Stress in the Thymus of Down Syndrome Patients. Front Immunol.
2021;12:669893.
MYASTENİA GRAVİSTE TİYOL-DİSÜLFİT HOMEOSTAZİSİ
Yıl 2025,
Cilt: 15 Sayı: 3, 324 - 330, 15.09.2025
Mariam Kavakcı
,
Merve Okuyucu
,
Salim Neşelioğlu
,
Evren Yaşar
,
Özcan Erel
Öz
Amaç: Nöromüsküler iletimde bir işlev bozukluğu ile karakterize olan nöromüsküler kavşak bozuklukları (NKB), oksidatif stresle ilişkili olabilir. Bu çalışma, NKB'li (myastenia gravis) yetişkin hastalarda oksidatif stresin bir endeksi olarak tiyol-disülfit homeostazının rolünü, bir biyobelirteç ve terapötik hedef olarak potansiyelini göz önünde bulundurarak sağlıklı kontrollerle karşılaştırmayı amaçlamıştır.
Gereç ve Yöntemler: Bu çalışmaya myastenia gravis tanılı 46 hasta ve yaş ve cinsiyet açısından eşleştirilmiş 46 sağlıklı kontrol dahil edildi. Kan örnekleri toplandı ve tiyol-disülfid homeostazisi parametreleri, toplam antioksidan durumu (TAS) ve iskemi ile modifiye edilmiş albümin (IMA) açısından spektrofotometrik ve kolorimetrik yöntemler kullanılarak analiz edildi. Grupları karşılaştırmak ve oksidatif ve antioksidan belirteçler arasındaki korelasyonları incelemek için SPSS kullanılarak istatistiksel analiz yapıldı.
Bulgular: Hastalar, kontrollere kıyasla önemli ölçüde daha düşük doğal tiyol, toplam tiyol ve TAS seviyeleri ve daha yüksek disülfit, disülfit/doğal tiyol yüzde oranı ve IMA seviyeleri gösterdi (tümü için p<0.05). Bu bulgular myastenia gravis tanısı olan hastalarda oksidatif stresin arttığını ve antioksidan savunmanın bozulduğunu göstermektedir. Azalan antioksidan parametreler ile artan oksidatif stres belirteçleri arasında da anlamlı korelasyonlar vardı.
Sonuç: Bu çalışma, myastenia gravis tanısı olan hastalarda tiyol-disülfit homeostazisinin önemli ölçüde değiştiğini doğrulayarak, bunun hastalık patogenezi için bir biyobelirteç ve terapötik müdahale için bir hedef olarak potansiyel rolünü vurgulamaktadır. NKB’li hastalarda redoks dengesini yeniden sağlamayı amaçlayan hedefe yönelik tedaviler geliştirmek için bu bulgular üzerinde daha fazla araştırma yapılabilir.
Kaynakça
-
1. Punga AR, Maddison P, Heckmann JM, Guptill JT, Evoli A.
Epidemiology, diagnostics, and biomarkers of autoimmune
neuromuscular junction disorders. Lancet Neurol 2022; 21(2):176-
88.
-
2. Mercuri E, Bönnemann CG, Muntoni F. Muscular dystrophies.
Lancet 2019; 394(10213):2025-38.
-
3. Verma S, Khurana S, Vats A, Sahu B, Ganguly NK, Chakraborti P,
et al. Neuromuscular junction dysfunction in amyotrophic lateral
sclerosis. Mol Neurobiol 2022; 59(3):1502-27.
-
4. Hehir MK, Silvestri NJ. Generalized myasthenia gravis: classification,
clinical presentation, natural history, and epidemiology. Neurol Clin.
2018; 36(2):253-60.
-
5. Tannemaat MR, Huijbers MG, Verschuuren JJGM. Myasthenia
gravis-pathophysiology, diagnosis, and treatment. Handb Clin
Neurol. 2024; 200:283-305.
-
6. Panpallı Ateş M. Clinical features of myasthenia gravis patients’:
The assessment of 138 patients. J Contemp Med. September 2021;
11(5):694-8.
-
7. Tekeşin A, Şişman Ç, Toprak UE, Sar A, Akalin B, Koşargelir G, et
al. Evaluation of nonmotor symptoms in myasthenia gravis patients.
Turk J Med Sci. 2024; 55(1):127-39.
-
8. Öncel S, Tunç A. Unveiling myasthenia gravis: A comprehensive
analysis of diagnostic tools and clinical insights. diclemedj. 2023;
50(4):482-9.
-
9. Aydın S, Kethüdaoğlu MO, Göçen HB, Albayrak HE, Köseoğlu A,
Altunok MK, et al. Effects of treatments applied in myasthenia gravis
on gait: Review. IGUSABDER. 2024; 459–67.
-
10. Dobrowolny G, Barbiera A, Sica G, Scicchitano BM. Age-related
alterations at neuromuscular junction: role of oxidative stress and
epigenetic modifications. Cells. 2021; 10(6):1307.
-
11. Jomova K, Raptova R, Alomar SY, Alwasel SH, Nepovimova E,
Kuca K, et al. Reactive oxygen species, toxicity, oxidative stress,
and antioxidants: chronic diseases and aging. Arch of Toxicol 2023;
97(10):2499-574.
-
12. Ionescu-Tucker A, Cotman CW. Emerging roles of oxidative
stress in brain aging and Alzheimer's disease. Neurobiol Aging 2021;
107:86-95.
-
13. Spaas J, van Veggel L, Schepers M, Tiane A, van Horssen J,
Wilson DM 3rd, et al. Oxidative stress and impaired oligodendrocyte
precursor cell differentiation in neurological disorders. Cell Mol Life
Sci 2021; 78(10):4615-37.
-
14. Teleanu DM, Niculescu AG, Lungu II, Radu CI, Vladâcenco O, Roza
E, et al. An overview of oxidative stress, neuroinflammation, and
neurodegenerative diseases. Int J Mol Sci 2022;25;23(11):5938.
-
15. Hajam YA, Rani R, Ganie SY, Sheikh TA, Javaid D, Qadri SS, et
al. Oxidative stress in human pathology and aging: Molecular
mechanisms and perspectives. Cells 2022;5;11(3):552.
-
16. González-Jamett A, Vásquez W, Cifuentes-Riveros G, MartínezPando R, Sáez JC, Cárdenas AM. Oxidative Stress, Inflammation and
Connexin Hemichannels in Muscular Dystrophies. Biomedicines.
2022;21;10(2):507.
-
17. Erel Ö, Erdoğan S. Thiol-disulfide homeostasis: an integrated
approach with biochemical and clinical aspects. Turk J Med Sci 2020;
50(SI-2):1728-38.
-
18. Ergin M, Aydin C, Yurt EF, Cakir B, Erel O. The variation of disulfides
in the progression of type 2 diabetes mellitus. Exp Clin Endocrinol
Diabetes 2020; 128(2):77-81.
-
19. Erzin G, Özkaya G, Topçuoğlu C, Yüksel RN, Erel, Ö, Yurt EF, et al.
Thiol/disulfide homeostasis in bipolar and unipolar depression. Clin
Psychopharmacol Neurosci 2020; 18(3):395-401.
-
20. Caliskan HM, Sivri S, Sokmen E, Celik M, Ilanbey B, Ozbek SC,
et al. Prognostic value of thiol/disulfide homeostasis in symptomatic
patients with heart failure. Arch Physiol Biochem 2021; 127(5):462-
7.
-
21. Güngör İ, Erdem AB, Kavaklı HŞ, Kösem A, Erel Ö, Neşelioğlu S.
Evaluation of thiol-disulfide homeostasis and ischemia-modified
albumin levels in patients presenting to the emergency department
in the postictal period. Turk Noroloji Derg. 2023; 29(2):118–25.
-
22. Sezgin B, Kinci MF, Pirinççi F, Camuzcuoğlu A, Erel Ö, Neşelioğlu S,
et al. Thiol-disulfide status of patients with cervical cancer. J Obstet
Gynaecol Res 2020; 46(11):2423-9.
-
23. Şener MU, Sönmez Ö, Keyf İA, Erel Ö, Alışık M, Bulut S, et al.
Evaluation of thiol/disulfide homeostasis in lung cancer. Turk Thorac
J 2020; 21(4):255-60.
-
24. 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.
-
25. Erel O, Neselioglu S. A novel and automated assay for thiol/
disulphide homeostasis. Clin Biochem 2014; 47(18):326-32.
-
26. Erel O. A novel automated direct measurement method for
total antioxidant capacity using a new generation, more stable ABTS
radical cation. Clin Biochem 2004; 37(4):277-85.
-
27. 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.
-
28. Alqahtani T, Deore SL, Kide AA, Shende BA, Sharma R, Dadarao
Chakole R, et al. Mitochondrial dysfunction and oxidative stress
in Alzheimer's disease, and Parkinson's disease, Huntington's
disease and Amyotrophic Lateral Sclerosis -An updated review.
Mitochondrion 2023; 71:83-92.
-
29. Cunha-Oliveira T, Montezinho L, Mendes C, Firuzi O, Saso
L, Oliveira PJ, et al. Oxidative Stress in Amyotrophic Lateral
Sclerosis: Pathophysiology and Opportunities for Pharmacological
Intervention. Oxid Med Cell Longev. 2020;2020:5021694.
-
30. Melms A, Schalke BC, Kirchner T, Müller-Hermelink HK, Albert E,
Wekerle H. Thymus in myasthenia gravis. Isolation of T-lymphocyte
lines specific for the nicotinic acetylcholine receptor from thymuses
of myasthenic patients. J Clin Invest 1988; 81(3):902-8.
-
31. Marcovecchio GE, Ferrua F, Fontana E, Beretta S, Genua M,
Bortolomai I, et al. Premature Senescence and Increased Oxidative
Stress in the Thymus of Down Syndrome Patients. Front Immunol.
2021;12:669893.