Taurin katkı maddesinin kalsiyum oksalat kristalizasyonuna etkisi

Öz

Böbrek taşları dünya nüfusunun % 8-15’ini etkileyen yaygın bir hastalık olup, kalsiyum oksalat kristalleri bu taşların temel bileşenini oluşturmaktadır. Yapılan mevcut çalışmalar kalsiyum oksalat kristallerinin oluşumunun değişik türdeki inorganik, organik ve biyolojik katkı maddelerinin kullanılmasıyla engellenebileceğini ortaya koymuştur. Bu çalışmada, kalsiyum oksalat kristallerinin yapı, morfoloji, tane boyutu, aglomerasyon eğilimleri gibi fiziksel özelliklerinin, taurin katkı maddesi kullanarak değiştirilmesi ve birikiminin engellenmesi amaçlanmaktadır. Bu kapsamda, ilk olarak sulu çözelti ortamında reaktif kristalizasyon yöntemi kullanılarak farklı taurin konsantrasyonunda kalsiyum oksalat kristalleri üretilmiştir. Daha sonra aynı deneyler sentetik üre ortamında gerçekleştirilmiştir. XRD ve FTIR analiz sonuçları, sulu çözelti ortamında üretilen kalsiyum oksalat kristallerinin termodinamik olarak en kararlı form olan monoklinik kalsiyum oksalat monohidrat (COM) yapısında olduğunu, sentetik üre ortamında elde edilen kristallerin ise tetragonal yapıdaki kalsiyum oksalat dihidrat (COD) kristalleri olduğunu göstermiştir. Bu sonuç, termogravimetrik analiz sonuçları ile desteklenmiş ve kristallerinin hidrat yapıları doğrulanmıştır. SEM analiz sonuçları, hem sulu çözelti ortamında elde edilen hekzagonal COM kristallerinin hem de sentetik üre ortamında üretilen bipiramidal COD kristallerinin morfolojilerinin ve aglomerasyon eğilimlerinin taurin varlığında değiştiğini göstermiştir. Ayrıca yapılan tane boyutu analiz sonuçları kristallerin tane boyutlarının taurin konsantrasyonunun artışına bağlı olarak önemli ölçüde küçüldüğünü göstermiştir. Sentetik üre ortamında üretilen COD kristallerinin tane boyutu 29 µm iken, bu değer 100 ppm taurin varlığında 11 µm olarak ölçülmüştür. Ayrıca, COM ve COD kristallerin yüzey yükleri zeta potansiyeli analiz yöntemiyle belirlenmiş ve katkı maddesi kullanımı hem COM hem de COD kristallerinin yüzey yüklerinin daha negatif bir değere ulaşmasını sağlamıştır. Bu çalışmanın, böbrek taşının oluşumunun inhibite edilmesi ve yavaşlatılmasına yönelik yapılacak araştırmalara katkı sağlayacağı düşünülmektedir.

Anahtar Kelimeler

• Kalsiyum oksalat
• kristalizasyon
• morfoloji
• böbrek taşı
• taurin

Effect of taurine additive on calcium oxalate crystallization

Öz

Kidney stones are a common disease affecting 8-15% of the world population, and calcium oxalate crystals constitute the main component of these stones. Current studies have shown that the formation of calcium oxalate crystals can be prevented using various types of inorganic, organic and biological additives. This study aims to change the physical properties of calcium oxalate crystals such as structure, morphology, particle size and agglomeration tendency and to prevent their accumulation using taurine as an additive. In this context, calcium oxalate crystals were produced in the absence and presence of three different taurine concentrations using the reactive crystallization method in an aqueous solution media. Then, the same experiments were carried out in synthetic urine. XRD and FTIR analysis results showed that calcium oxalate crystals obtained in aqueous solution were in the form of monoclinic calcium oxalate monohydrate (COM), which is the most thermodynamically stable form, while the crystals obtained in synthetic urine were in the form of tetragonal calcium oxalate dihydrate (COD). This result was supported by thermogravimetric analysis results and the hydrate structures of the crystals were determined. SEM analysis results showed that the morphology and agglomeration tendency of both hexagonal COM crystals obtained in aqueous solution and bipyramidal COD crystals produced in synthetic urine changed in the presence of taurine. The particle size analysis results showed that the size of the crystals decreased significantly depending on the increase in taurine concentration. While the particle size of COD crystals obtained in synthetic urine was 29 µm, this value was 11 µm in the presence of 100 ppm taurine. In addition, the surface charges of COM and COD crystals were determined by zeta potential analysis and it was determined that the use of additive made the surface charges of both COM and COD crystals more negative. In conclusion, we hope this study will contribute to the research to be conducted on inhibiting the formation of kidney stones.

Anahtar Kelimeler

• Calcium oxalate
• crystallization
• morphology
• kidney stone
• taurine.

Kaynakça

1. Peerapen, P. ve Thongboonkerd, V., Differential bound proteins and adhesive capabilities of calcium oxalate monohydrate crystals with various sizes, Int. J. Biol. Macromol., 163, 2210-2223, (2020).
2. Masao, T., Mechanism Of Calcium Oxalate Renal Stone Formation And Renal Tubular Cell Injury, International Journal of Urology, 15, 115–120, (2008).
3. Chatterjee, P., Chakraborty, A. ve Mukherjee, A.K., Phase Composition and Morphological Characterization of Human Kidney Stones Using IR Spectroscopy, Scanning Electron Microscopy and X-Ray Rietveld Analysis, Spectrochim. Acta - Part A Mol. Biomol. Spectrosc., 200, 33-42, (2018).
4. Liu, Y., Chen, S., Liu, J., Jin, Y., Yu, S. ve An, R., Telmisartan Inhibits Oxalate and Calcium Oxalate Crystal-Induced Epithelial-Mesenchymal Transformation via PPAR-γ-AKT/STAT3/P38 MAPK-Snail Pathway, Life Sci., 241, 117108, (2020).
5. Wang, X., Wang, M., Ruan, J., Zhao, S., Xiao, J. ve Tian, Y., Identification of Urine Biomarkers for Calcium-Oxalate Urolithiasis in Adults Based on UPLC-Q-TOF/MS., J. Chromatogr. B Anal. Technol. Biomed. Life Sci., 1124, 290–297, (2019).
6. Smith, L.H., The Many Roles of Oxalate in Nature, Trans. Am. Clin. Climatol. Assoc., 113, 1–20, (2002).
7. McMulkin, C.J., Massi, M., Jones, F., Tetrazoles: Calcium Oxalate Crystal Growth Modifiers, CrystEngComm, 17, 2675–2681, (2015).
8. Ibis, F., Dhand, P., Suleymanli, S., Van Der Heijden, A.E.D.M., Kramer, H.J.M., Eral, H.B., A Combined Experimental and Modelling Study on Solubility of Calcium Oxalate Monohydrate at Physiologically Relevant pH and Temperatures, Crystals, 10, 924, (2020).

9. Tazzoli, V.; Domeneghetti, C., The Crystal Structures of Whewellite and Weddellite: Re-Examination and Comparison, Am. Mineral., 65, 327-334, (1980).
10. Oner, M., Koutsoukos, P.G. ve Robertson, W.G., Kidney Stone Formation- Thermodynamic, Kinetic, And Clinical Aspects, Water-Formed Deposits Fundamentals and Mitigation Strategies, 511-541, (2022).
11. Wesson, J.A., Ward, M.D., Pathological Biomineralization of Kidney Stones, Elements, 3, 415–421, (2007).
12. Deganello, S., Kampf, A.R., Moore, P.B., The Crystal Structure of Calcium Oxalate Trihydrate: Ca(H2O)3(C2O4)., Am. Mineral., 66, 859–865, (1981).
13. Conti, C., Casati, M., Colombo, C., Possenti, E., Realini, M., Gatta, G.D., Merlini, M., Brambilla, L. ve Zerbi, G., Synthesis of Calcium Oxalate Trihydrate: New Data by Vibrational Spectroscopy and Synchrotron X-Ray Diffraction. Spectrochim. Acta - Part A Mol. Biomol. Spectrosc., 150, 721-730, (2015).
14. Barker, T., Boon, M. ve Jones, F., The Role of Zinc Ions in Calcium Oxalate Monohydrate Crystallization, Journal of Crystal Growth, 546, 125777, (2020).
15. Zhang, J., Wang, L., Zhang, W. ve Putnis, C.V., Role of Hyperoxaluria/Hypercalciuria in Controlling the Hydrate Phase Selection of Pathological Calcium Oxalate Mineralization, Crystal Growth Design, 21, 683–691, (2021).
16. Saha, S. ve Mishra, A., A Facile Preparation of Rutin Nanoparticles and Its Effects on Controlled Growth and Morphology of Calcium Oxalate Crystals, J Journal of Crystal Growth, 540, 125635, (2020).
17. Moe, O.W., Pearle, M.S. ve Sakhaee, K. Pharmacotherapy of Urolithiasis: Evidence from Clinical Trials, Kidney Int., 79, 385-392, (2011).
18. Ramaswamy, K., Killilea, D.W., Kapahi, P., Kahn, A.J., Chi, T. ve Stoller, M.L. The Elementome of Calcium-Based Urinary Stones and Its Role in Urolithiasis, Nat Rev Urol., 12, 543–557, (2015).
19. Huang, L.S., Sun, X.Y., Gui, Q. ve Ouyang, J.M., Effects of Plant Polysaccharides with Different Carboxyl Group Contents on Calcium Oxalate Crystal Growth, CrystEngComm, 19, 4838–4847, (2017).
20. Golovanova, O.A. ve Korolkov, V.V., Effect of Amino Acids on the Crystallization Kinetics of Calcium Oxalate Monohydrate, Chemistry for Sustainable Development, 21, 381–388, (2013).
21. Golovanova, O.A. ve Korolkov, V.V., Thermodynamics and Kinetics of Calcium Oxalate Crystallization in the Presence of Amino Acids, Crystallogr. Reports, 62, 787-796, (2017).
22. Taranets, Y.V., Bezkrovnaya, O. N. ve Pritula, I.M., Effect of Amino Acids and B-Group Vitamins on Nucleation of Calcium Oxalate Monohydrate Crystals, Journal of Crystal Growth, 531, 125368, (2020).
23. He, J., Lin, R., Long, H., Liang, Y. ve Chen, Y., Adsorption Characteristics of Amino Acids on to Calcium Oxalate, J. Colloid Interface Sci, 454, 144-151, (2015).
24. Gul, A. ve Rez, P., Models for Protein Binding to Calcium Oxalate Surfaces, Urol. Res., 35, 63-71, (2007).
25. Narula, S., Tandon, S., Singh, S.K. ve Tandon, C., Kidney Stone Matrix Proteins Ameliorate Calcium Oxalate Monohydrate Induced Apoptotic Injury to Renal Epithelial Cells, Life Sci., 164, 23-30, (2016).
26. Li, S., Tang, W., Shi, P., Li, M., Sun, J. ve Gong, J., A New Perspective of Gallic Acid on Calcium Oxalate Nucleation, Crystal Growth Design, 20, 3173-3181, (2020).
27. Li, S., Tang, W., Li, M., Wang, L., Yang, Y. ve Gong, J., Understanding the Role of Citric Acid on the Crystallization Pathways of Calcium Oxalate Hydrates, Crystal Growth Design, 19, 3139-3147, (2019).
28. Ouyang, J.M., Duan, L. ve Tieke, B., Effects of Carboxylic Acids on the Crystal Growth of Calcium Oxalate Nanoparticles in Lecithin-Water Liposome Systems, Langmuir, 19 (21), 8980–8985, (2003).
29. Akyol, E. ve Öner, M., Controlling of morphology and polymorph of calcium oxalate crystals by using polyelectrolytes, Journal of Crystal Growth, 401, 260-265, (2014).
30. Akyol, E., Ongun, K., Kirboga, S. ve Öner, M., A Kinetic Study for Calcium Oxalate Crystallization in the presence of Viburnum Opulus Extract, Biointerface Research in Applied Chemistry, 6, 1064-1069, (2016).
31. Han, X., Patters, A.B., Jones, D., Zelikovic, I., ve Chesney, R.W., The taurine transporter: mechanisms of regulation, Acta Physiologica, 187(1-2), 61-73, (2006).
32. Allard, M.L., Jeejeebhoy, K.N., ve Sole, M.J., The management of conditioned nutritional requirements in heart failure, Heart Failure Reviews, 11(1), 75-82, (2006).
33. Wu, J. ve Prentice, H., Role of taurine in the central nervous system, Journal of Biomedical Science, 17(Suppl 1), S1. (2010).
34. Chen, W., Ji, H., Nguyen, M.L., Carr, J.A., Lee, Y., Hsu, C. Ve Wu, J. Y. Role of taurine in regulation of intracellular calcium level and neuroprotective function in cultured neurons, Journal of Neuroscience Research, 66(4), 612-619. (2001).
35. Ren, F., Liu, X., Liu, X., Cao, Y., Liu, L., Li, X., ve Hu, J. In vitro and in vivo study on prevention of myocardial ischemic injury by taurine. Annals of Translational Medicine, 9(12), 984-984. (2021).
36. Sun, Y., Dai, S., Tao, J., Li, Y., He, Z., Liu, Q., Zhao, J., Deng, Y., Kang, J., Zhang, X., Yang, S. ve Liu, Y., Taurine suppresses ROS-dependent autophagy via activating Akt/mTOR signalling pathway in calcium oxalate crystals-induced renal tubular epithelial cell injury, Aging (Albany NY), 12(17), 17353-17366, (2020).