Bazı Yapay Gözyaşı Damlalarının İnsan Karbonik Anhidraz Enzimi-II (hCA-II) Üzerindeki İnhibitör Etkileri

Yıl 2023, Cilt: 13 Sayı: 2, 941 - 947, 01.06.2023

Büşra Çalışkan , Mine Aksoy

https://doi.org/10.21597/jist.1253344

Öz

Karbonik anhidrazlar (CA), canlılarda karbondioksitin hidrasyonu ve bikarbonat anyonunun dehidrasyonu reaksiyonlarını tersinir olarak katalize eden, aktif bölgelerinde çinko iyonları içeren bir metalloenzimdir. Bu çalışmada, insan eritrositlerinden karbonik anhidraz II (hCAII),
afinite (sefaroz 4B/L-tirozin-sülfanilamid) kolonu ile saflaştırıldı. Yapay gözyaşı damlalarının hCAII izoenzimi üzerindeki inhibitör etkisi araştırıldı. IC50 değerleri sodyum hiyalüronat için 1.01 µL, polivinil alkol+povidon için 140.06 µL, polietilen glikol+propilen glikol için 49.51
µL olarak hesaplandı. Sodyum hiyalüronat için Ki değeri 0.339±0.121 mM olarak bulundu. Bu sonuçlara göre, incelenen üç ilaç arasında uygulama hacmi (mikrolitre) açısından en etkili inhibitörün sodyum hiyalüronat olduğu görülmektedir.

Anahtar Kelimeler

İnsan karbonik anhidraz II, Suni gözyaşı damlaları, İnhibisyon

Inhibitor Effects of Some Artificial Tears Drops on Human Carbonic Anhydrase Enzyme-II (hCA-II)

Öz

Carbonic anhydrases (CAs) are a metalloenzyme that contains zinc ions in their active sites, and they reversibly catalyze the reactions of hydration of CO2 and dehydration of HCO3-in the living. In this study, human carbonic anhydrase II (hCAII) isoenzyme was purified from human erythrocytes by affinity column (Sepharose 4B-L-tyrosine-sulfanilamide). The inhibitory effect of artificial tear drops on hCAII isoenzyme was investigated. IC50 values were calculated as 1.01 µL for sodium hyaluronate, 140.06 µL for polyvinyl alcohol+povidone, and 49.51 for polyethylene glycol+propylene glycol. The Ki value for sodium hyaluronate was found as 0.339±0.121 mM. According to these results, sodium hyaluronate was the most effective inhibitor in terms of application volume (microliter) among the three drugs examined.

Anahtar Kelimeler

Carbonic anhydrase II, artificial tears drops, inhibition

Kaynakça

• Bromberg, B.B., Welch, M.H., Beuerman, R.W., Chew, S-J., Thompson, H.W., Ramage, D., Githens, S., (1993). Histochemical distribution of carbonic anhydrase in rat and rabbit lacrimal gland. Investigative Ophthalmology & Visual Science, 34: 339-348
• Bron, A. J., Tomlinson, A., Foulks, G. N., Pepose, J. S., Baudouin, C., Geerling, G., ... & Lemp, M. A. (2014). Rethinng dry eye disease: a perspective on clinical implications. The Ocular Surface, 12(2), S1-S31.
• Candia, O.A., (1996). A novel system to measure labelled CO2 and HCO3 fluxes across epithelia: corneal epithelium as model tissue. Experimental Eye Research, 63:137–149
• Carradori S, Mollica A, De Monte C, Ganese A, Supuran CT. (2015) Nitric oxide donors and selective carbonic anhydrase inhibitors: a dual pharmacological approach for the treatment of glaucoma, cancer and osteoporosis. Molecules, 20:5667-5679.
• Cerdà‐Costa, N., & Xavier Gomis‐Rüth, F., (2014). Architecture and function of metallopeptidase catalytic domains. Protein Science, 23(2), 123-144.
• Craig, J.P., Nelson, J.D., Azar, D.T., (2017). TFOS DEWS II Report Executive Summary. Ocular Surface,15(4):802–812.
• Cui, N., Hu, M., & Khalil, R. A. (2017). Biochemical and biological attributes of matrix metalloproteinases. Progress in Molecular Biology and Translational Science, 147, 1-73.
• Erb, C., Gast, U., & Schremmer, D. (2008). German register for glaucoma patients with dry eye. I. Basic outcome with respect to dry eye. Graefe's Archive for Clinical and Experimental Ophthalmology, 246, 1593-1601.
• Kuppens, E. V., VAN BEST, J. A., Sterk, C. C., & DE KEIZER, R. J. (1995). Decreased basal tear turnover in patients with untreated primary open-angle glaucoma. American Journal of Ophthalmology, 120(1), 41-46.
• Labetoulle, M., Benitez-del-Castillo, J. M., Barabino, S., Herrero Vanrell, R., Daull, P., Garrigue, J. S., & Rolando, M. (2022). Artificial tears: biological role of their ingredients in the management of dry eye disease. International Journal of Molecular Sciences, 23(5), 2434.
• Laemelli, D. (1970). Cleavage of structural proteins during in assembly of the head of bacteriophage. Nature, 15;227(5259):680.
• Leung, E. W., Medeiros, F. A., & Weinreb, R. N. (2008). Prevalence of ocular surface disease in glaucoma patients. Journal of Glaucoma, 17(5), 350-355.
• Lanza, N. L., Valenzuela, F., Perez, V. L., & Galor, A. (2016). The matrix metalloproteinase 9 point-of-care test in dry eye. The Ocular Surface, 14(2), 189-195.
• Messmer EM, (2015). The pathophysiology, diagnosis and treatment of dry eye disease. Deutsches Arzteblatt International, 112: 71–82.
• Milner, M. S., Beckman, K. A., Luchs, J. I., Allen, Q. B., Awdeh, R. M., Berdahl, J., ... & Yeu, E. (2017). Dysfunctional tear syndrome: dry eye disease and associated tear film disorders–new strategies for diagnosis and treatment. Current Opinion in Ophthalmology, Jan;27 Suppl 1(Suppl 1):3-47.
• Mincione F, Scozzafava A, Supuran CT. (2007) The development of topically acting carbonic anhydrase inhibitors as anti-glaucoma agents. Current Topics in Medicinal Chemistry, 7:849-854.
• Nalbantoğlu, B., Demir, N., Özdemir, H., & Küfrevioğlu, Ö. İ. (1996). A new method for the purification of carbonic anhydrase isozymes by affinity chromatography. Turkish Journal of Medical Sciences, 21, 159–162.
• Ogawa Y, Toyosawa S, Inagaki T, Hong SS, Ijuhin N, (1995). Carbonic anhydrase VI in rat lacrimal gland. Histochemistry and Cell Biology, 103: 387-394
• Parham Taslimi, Ilhami Gulcin, Bunyamin Ozgeris, Suleyman Goksu, Ferhan Tumer, Saleh H. Alwasel & Claudiu T. Supuran (2016). The human carbonic anhydrase isoenzymes I and II (hCA I and II) inhibition effects of trimethoxyindane derivatives, Journal of Enzyme Inhibition and Medicinal Chemistry, 31:1, 152-157
• Pflugfelder, S. C., & de Paiva, C. S. (2017). The pathophysiology of dry eye disease: what we know and future directions for research. Ophthalmology, 124(11), S4-S13.
• Richichi, B., Baldoneschi, V., Burgalassi, S., Fragai, M., Vullo, D., Akdemir, A, & Nativi, C. (2016). A divalent PAMAM‐based matrix metalloproteinase/carbonic anhydrase inhibitor for the treatment of dry eye syndrome. Chemistry–A European Journal, 22(5), 1714-1721.
• Rossi, G. C. M., Tinelli, C., Pasinetti, G. M., Milano, G., & Bianchi, P. E. (2009). Dry eye syndrome-related quality of life in glaucoma patients. European Journal of Ophthalmology, 19(4), 572-579.
• Scozzafava A, Supuran CT. (2014) Glaucoma and the applications of carbonic anhydrase inhibitors. Subcell Biochemistry, 75:349-359.
• Stern ME, Schaumburg CS, Pflugfelder SC, (2013). Dry eye as a mucosal autoimmune disease. International Reviews of Immunology, 32: 19–41
• Sugrue MF. (2000) Pharmacological and ocular hypotensive properties of topical carbonic anhydrase inhibitors. Progress in Retinal and Eye Research, 19:87-112.
• Supuran, C. T., & De Simone, G. (Eds.). (2015). Carbonic anhydrases as biocatalysts: from theory to medical and industrial applications. Elsevier.
• Supuran, C. T., Altamimi, A. S. A., & Carta, F. (2019). Carbonic anhydrase inhibition and the management of glaucoma: a literature and patent review 2013-2019. Expert Opinion on Therapeutic Patents, 29(10), 781-792.
• Verpoorte, J. A., Mehta, S., & Edsall, J. T. (1967). Esterase activities of human carbonic anhydrases B and C. Journal of Biological Chemistry, 242, 4221–4229.
• Wei, Y., & Asbell, P. A. (2014). The core mechanism of dry eye disease (DED) is inflammation. Eye & Contact Lens, 40(4), 248.
• Wilbur, K. M., & Anderson, N. G. (1948). Electrometric and colorimetric determination of carbonic anhydrase. Journal of Biological Chemistry, 176(1), 147–154.
• Wistrand, P. J. (2000). Carbonic anhydrase inhibition in ophthalmology: carbonic anhydrases in cornea, lens, retina and lacrimal gland. EXS. 2000;(90):413-24.