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The Role of Thiosulfate Sulfurtransferase in Oxidative Stress for Type 2 Diabetes Mellitus

https://doi.org/10.14341/DM13279

Abstract

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with oxidative stress, leading to insulin resistance. Thiosulfate sulfurtransferase (TST) is mitochondrial enzyme involved in the reaction with cyanide, endogenous hydrogen sulfide (H₂S), and reactive oxygen species.

AIM: This study aimed to investigate the relationship between TST enzyme and both oxidative and anti-oxidative stress markers in T2DM patients. TST is believed to be related to oxidative stress, which plays a crucial role in determining the severity and progression of the disease.

MATERIALS AND METHODS: A case-control study included (150) T2DM patients who were taking the drug Metformin (Glucophage) 500 mg twice daily as well as (150) healthy subjects aged between 33 to 65 years. TST activity was estimated based on the sulfur transfer and thiocyanate formation. Malonaldehyde (MDA), peroxynitrite, peroxidase, aryl esterase, vitamin C, vitamin E, thioredoxin (Trx) and glutathione (GSH) were also measured. In addition to clinical markers, all measurements were made in two replicates, statistical analyses were conducted, and data were presented as a median and interquartile range.

RESULTS: TST activity was significantly lower (by 55%) in T2DM patients compared to the controls (8.5 (3.8) vs. 19 (2) U/ml, respectively). There was an inverse relationship between enzyme activity and age, whereas enzyme activity increased with smoking. Antioxidant compounds such as vitamin C, vitamin E, GSH, Trx, and arylesterase activity were significantly lower, while oxidant markers including peroxidase activity, MDA, and peroxynitrite, were significantly higher. TST activity showed a negative correlation with MDA and peroxynitrite, and a positive correlation with Trx and GSH.

CONCLUSION: TST activity is reduced in T2DM patients and is associated with oxidative stress. This suggest that TST may play a protective role against oxidative stress, making it a potential indicator of metabolic regulation and a possible therapeutic target.

About the Authors

M. M. Mawajdeh
University of Mosul
Iraq

Marwa M. Mawajdeh - Master’s student in Biochemistry.

Mosul


Competing Interests:

None



T. A. Allwsh
University of Mosul
Iraq

Thikra A. Allwsh - Professor, PhD in Biochemistry; ResearcherID: https://www.researchgate.net/profile/Thikra-Allwsh; Scopus Author ID: 57226087609.

Iraq, Mosul, Al-Zahraa Street, 41003


Competing Interests:

None



References

1. International Diabetes Federation. (2023). IDF Diabetes Atlas (10th ed.). International Diabetes Federation. https://diabetesatlas.org

2. Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K. B., ... & Martín, C. (2020). Pathophysiology of type 2 diabetes mellitus. International journal of molecular sciences, 21(17), 6275.‏

3. Vona, R., Pallotta, L., Cappelletti, M., Severi, C., & Matarrese, P. (2021). The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders. Antioxidants (Basel, Switzerland), 10(2), 201. https://doi.org/10.3390/antiox10020201

4. Pasupuleti, V. R., Arigela, C. S., Gan, S. H., Salam, S. K. N., Krishnan, K. T., Rahman, N. A., & Jeffree, M. S. (2020). A Review on Oxidative Stress, Diabetic Complications, and the Roles of Honey Polyphenols. Oxidative medicine and cellular longevity, 2020, 8878172. https://doi.org/10.1155/2020/8878172

5. Yaribeygi, H., Sathyapalan, T., Atkin, S. L., & Sahebkar, A. (2020). Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus. Oxidative medicine and cellular longevity, 2020, 8609213. https://doi.org/10.1155/2020/8609213

6. Charlton, A., Garzarella, J., Jandeleit-Dahm, K. A., & Jha, J. C. (2020). Oxidative stress and inflammation in renal and cardiovascular complications of diabetes. Biology, 10(1), 18.‏

7. Chaudhary M, Gupta R. Cyanide detoxifying enzyme: Rhodanese. Curr. Biotechnol. e. 2012;1:327–335. doi: 10.2174/2211550111201040327. [CrossRef] [Google Scholar]

8. Morton, N., Beltram, J., Carter, R. et al. Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness. Nat Med 22, 771–779 (2016). https://doi.org/10.1038/nm.4115[PMC free article] [PubMed] [CrossRef] [Google Scholar]

9. Al-Dahmani ZM, Hadian M, Ruiz-Moreno AJ, Maria S-GA, Batista FA, Zhang R, et al. Identification and characterization of a small molecule that activates thiosulfate sulfurtransferase and stimulates mitochondrial respiration. Protein Science. 2023; 32(11):e4794. https://doi.org/10.1002/pro.4794

10. Kruithof, P. D., Lunev, S., Lozano, S. P. A., de Assis Batista, F., Al-Dahmani, Z. M., Joles, J. A., ... & van Goor, H. (2020). Unraveling the role of thiosulfate sulfurtransferase in metabolic diseases. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1866(6), 165716.‏

11. https://doi.org/10.1016/j.bbadis.2020.165716.

12. Nandi, D. L., Horowitz, P. M., & Westley, J. (2000). Rhodanese as a thioredoxin oxidase. The international journal of biochemistry & cell biology, 32(4), 465–473. https://doi.org/10.1016/s1357-2725(99)00035-7

13. Urbanska, K., Wiater, A., & Nowak, A. (2002). Thiosulfate sulfurtransferase activity in rat tissues in the presence of organic nitriles. Acta Biochimica Polonica, 49(1), 109-114.

14. Saadon, S.R., & Allwsh, T.A. (2024). A CLINICAL STUDY OF LIPOCALIN 2 AND ITS RELATION WITH OXIDATIVE AND ANTIOXIDATIVE FACTORS IN ARTHRITIS. MMSL, 93(4), 335-341. doi: 10.31482/mmsl.2023.040.

15. Arnér, E. S. J., L. Zhong, A. Holmgren, and P. Lester. (1999). Preparation and assay of mammalian thioredoxin and thioredoxin reductase. Methods Enzymol. 300:226-239. https://doi.org/10.1016/S0076-6879(99)00129-9.

16. Perridon, B. W., Leuvenink, H. G., Hillebrands, J. L., van Goor, H., & Bos, E. M. (2016). The role of hydrogen sulfide in aging and age-related pathologies. Aging, 8(10), 2264–2289. https://doi.org/10.18632/aging.101026

17. Szlęzak, D., Bronowicka-Adamska, P., Hutsch, T., Ufnal, M., & Wróbel, M. (2021). Hypertension and Aging Affect Liver Sulfur Metabolism in Rats. Cells, 10(5), 1238. https://doi.org/10.3390/cells10051238

18. Luo, Y., Chatre, L., Melhem, S., Al-Dahmani, Z. M., Homer, N. Z. M., Miedema, A., Deelman, L. E., Groves, M. R., Feelisch, M., Morton, N. M., Dolga, A., & van Goor, H. (2023). Thiosulfate sulfurtransferase deficiency promotes oxidative distress and aberrant NRF2 function in the brain. Redox biology, 68, 102965. https://doi.org/10.1016/j.redox.2023.102965

19. San Gabriel, P. T., Liu, Y., Schroder, A. L., Zoellner, H., & Chami, B. (2020). The role of thiocyanate in modulating myeloperoxidase activity during disease. International Journal of Molecular Sciences, 21(17), 6450.‏

20. Mas-Bargues, C., Escriva, C., Dromant, M., Borras, C., & Vina, J. (2021). Lipid peroxidation as measured by chromatographic determination of malondialdehyde. Human plasma reference values in health and disease. Archives of biochemistry and biophysics, 709, 108941.‏

21. Najafi, A., Pourfarzam, M., & Zadhoush, F. (2021). Oxidant/antioxidant status in Type-2 diabetes mellitus patients with metabolic syndrome. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences, 26, 6. https://doi.org/10.4103/jrms.JRMS_249_20

22. Newsholme, P., Keane, K. N., Carlessi, R., & Cruzat, V. (2019). Oxidative stress pathways in pancreatic β-cells and insulin-sensitive cells and tissues: importance to cell metabolism, function, and dysfunction. American Journal of Physiology-Cell Physiology, 317(3), C420-C433.‏

23. Bahadoran, Z., Mirmiran, P., Kashfi, K., & Ghasemi, A. (2023). Vascular nitric oxide resistance in type 2 diabetes. Cell Death & Disease, 14(7), 410.‏

24. Piacenza, L., Zeida, A., Trujillo, M., & Radi, R. (2022). The superoxide radical switch in the biology of nitric oxide and peroxynitrite. Physiological Reviews, 102(4), 1881-1906.‏

25. Bala, A. (2024). Regulatory role of peroxynitrite in advanced glycation end products mediated diabetic cardiovascular complications. World Journal of Diabetes, 15(3), 572.‏

26. Tuell, D., Ford, G., Los, E., & Stone, W. (2024). The Role of Glutathione and Its Precursors in Type 2 Diabetes. Antioxidants (Basel, Switzerland), 13(2), 184. https://doi.org/10.3390/antiox13020184

27. Stancill, J. S., & Corbett, J. A. (2021). The role of thioredoxin/peroxiredoxin in the β-cell defense against oxidative damage. Frontiers in Endocrinology, 12, 718235.‏

28. Xu, L. L., Gao, W., Chen, Z. M., Shao, K. K., Wang, Y. G., Cui, L. L., & Guo, N. Z. (2020). Relationships between diabetic nephropathy and insulin resistance, inflammation, Trx, Txnip, CysC and serum complement levels. European Review for Medical & Pharmacological Sciences, 24(22).‏

29. Kar, A., Paramasivam, B., Jayakumar, D., Swaroop, A. K., & Jubie, S. (2023). Thioredoxin Interacting Protein Inhibitors in Diabetes Mellitus: A Critical Review. Current Drug Research Reviews Formerly: Current Drug Abuse Reviews, 15(3), 228-240.

30. Liu, C., Dong, W., Lv, Z., Kong, L., & Ren, X. (2022). Thioredoxin-interacting protein in diabetic retinal neurodegeneration: A novel potential therapeutic target for diabetic retinopathy. Frontiers in neuroscience, 16, 957667. https://doi.org/10.3389/fnins.2022.957667

31. Averill-Bates, D. A. (2023). The antioxidant glutathione. In Vitamins and hormones (Vol. 121, pp. 109-141). Academic Press.‏ ‏

32. Nikzad, A., Alizadeh, A., Abediankenari, S., Kashi, Z., & Mahrooz, A. (2023). Paraoxonase 1 activity is associated with interleukin-6 levels in type 2 diabetes: Effects of age and gender. International Journal of Preventive Medicine, 14(1), 23.‏

33. Castañé, H., Jiménez-Franco, A., Martínez-Navidad, C., Placed-Gallego, C., Cambra-Cortés, V., Perta, A. M., ... & Joven, J. (2023). Serum Arylesterase, Paraoxonase, and Lactonase Activities and Paraoxonase-1 Concentrations in Morbidly Obese Patients and Their Relationship with Non-Alcoholic Steatohepatitis. Antioxidants, 12(12), 2038.‏

34. Marsillach, J., Richter, R. J., Costa, L. G., & Furlong, C. E. (2021). Paraoxonase-1 (PON1) Status Analysis Using Non-Organophosphate Substrates. Current protocols, 1(1), e25. https://doi.org/10.1002/cpz1.25

35. Razip, N. N. M., Gopalsamy, B., Abdul Mutalib, M. S., Chang, S. K., Abdullah, M. M. J. A., Azlan, A., Rejali, Z., & Khaza'ai, H. (2021). Correlation between Levels of Vitamins D3 and E in Type 2 Diabetes Mellitus: A Case-Control Study in Serdang, Selangor, Malaysia. Nutrients, 13(7), 2288. https://doi.org/10.3390/nu13072288

36. Hattiwale, S., Jargar, J. J., Hattiwale, H. R., Ahmed, M. M., & Nazeer, M. (2022). Status of non-enzymatic antioxidant vitamins (C and E) in patients either with type 2 diabete mellitus or hypertension alone and coexisted diabetes and hypertension. ACADEMIC JOURNAL.‏

37. Mc Fadden, C. E. (2018). Investigating the role of thiosulfate sulfurtransferase in adipose tissue dysfunction in obesity.‏

38. Melideo, S. L., Jackson, M. R., & Jorns, M. S. (2014). Biosynthesis of a central intermediate in hydrogen sulfide metabolism by a novel human sulfurtransferase and its yeast ortholog. Biochemistry, 53(28), 4739–4753. https://doi.org/10.1021/bi500650h

39. Libiad, M., Motl, N., Akey, D. L., Sakamoto, N., Fearon, E. R., Smith, J. L., & Banerjee, R. (2018). Thiosulfate sulfurtransferase-like domain-containing 1 protein interacts with thioredoxin. The Journal of biological chemistry, 293(8), 2675–2686. https://doi.org/10.1074/jbc.RA117.000826


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For citations:


Mawajdeh M.M., Allwsh T.A. The Role of Thiosulfate Sulfurtransferase in Oxidative Stress for Type 2 Diabetes Mellitus. Diabetes mellitus. 2025;28(4):359-366. https://doi.org/10.14341/DM13279

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