Sıvı kardiyak ilaçların karbonik anhidraz I ve II izoenzimleri üzerindeki etkileri

Abstract

Kardiyovasküler hastalıklar dünya çapında ölümlerin önde gelen nedenidir. Son yıllarda karbonik anhidraz inhibitörleri ile ateroskleroz arasındaki ilişki dikkat çekmektedir. Bu çalışmada, sık kullanılan sıvı kardiyak ilaçların insan karbonik anhidraz (hCA) I ve II üzerine in vitro etkilerini belirlemeyi amaçladık. İlaçların hCA I ve hCA II üzerindeki inhibitör etkileri hidrataz aktivitesi ile belirlendi. Test edilen kardiyak ilaçlarının tamamı hCA I ve II izozimlerini inhibine etmiştir. En güçlü inhibitörün Atropin Sülfat (hCA I: 5,86 mM ve hCA II: 6,59 mM) olduğunu saptadık. Heparin Sodyum ve Dopamin HCl de güçlü inhibitörlerdir.

Keywords

• Kardiyak ilaçlar
• karbonik anhidraz
• enzim inhibisyonu

Effects of liquid cardiac drugs on carbonic anhydrase I and II ısozymes

Abstract

Cardiovascular diseases are the leading cause of death worldwide. In recent years, the relationship between atherosclerosis and carbonic anhydrase inhibitors has attracted attention. In this study, we aimed to determine the in vitro effects of commonly used liquid cardiac drugs on human carbonic anhydrase (hCA) I and II. The inhibitory effects of drugs on hCA I and hCA II were determined by hydratase activity. All tested cardiac drugs inhibited hCA I and II isozymes. We found that the strongest inhibitor was Atropine sulfate (hCA I: 5.86 mM and hCA II: 6.59 mM). Heparin Sodium and Dopamine HCl are also potent inhibitors.

Keywords

• Cardiac drugs
• carbonic anhydrase
• enzyme inhibition

References

1. Supuran CT, Altamimi ASA, Carta F. Carbonic anhydrase inhibition and the management of glaucoma: a literature and patent review 2013–2019. Expert Opinion on Therapeutic Patents, 29:781–92, (2019).
2. Supuran CT. Carbonic anhydrase inhibitors. Bioorganic & Medicinal Chemistry Letters, 20:3467–74, (2010).
3. Nowbar AN, Gitto M, Howard JP, et al. Mortality from ischemic heart disease. Circulation: Cardiovascular Quality and Outcomes,12: e005375,(2019).
4. Gamble W. Atherosclerosis: the carbonic anhydrase, carbon dioxide, calcium concerted theory. Journal of Theoretical Biology, 239: 16–21, (2006).
5. Goodman WG, London G, Amann K, et al. Vascular calcification in chronic kidney disease. Am J. Kidney Diseases, 43: 572e579, (2000).
6. Ramanan R, Kannan K, Sivanesan S, et al. Bio-sequestration of carbon dioxide using carbonic anhydrase enzyme purified from Citrobacter freundii. World Journal of Microbiology and Biotechnology, 25: 981e987, (2009).
7. Adeva-Andany MM, Fernandez-Fernandez C, Sanchez-Bello R, et al. The role of carbonic anhydrase in the pathogenesis of vascular calcification in humans. Atherosclerosis, 241: 183–91, (2015).
8. Taskin MI, Bilen C, Ergun A, et al. In vitro effects of estrogen and progesterone containing drugs on human erythrocyte carbonic anhydrase I and II isozymes in women smokers and nonsmokers. Journal of the Chinese Medical Association, 78:513–9, (2015).

9. Sarıoglu N, Bilen C, Sackes Z, et al. The effects of bronchodilator drugs and antibiotics used for respiratory infection on human erythrocyte carbonic anhydrase I and II isozymes. Archives of Physiology and Biochemistry , 121:56–61, (2015).
10. Koc ER, Erken G, Bilen C, et al. The effects of anti-epileptic drugs on human erythrocyte carbonic anhydrase I and II isozymes. Archives of Physiology and Biochemistry , 120:131–5,(2014).
11. Erzengin M, Bilen C, Ergun A, et al. Antipsychotic agents screened as human carbonic anhydrase I and II inhibitors. Archives of Physiology and Biochemistry, 120:29–33, (2014).
12. Bozdag M, Isik S, Beyaztas S, et al. Synthesis of a novel affinity gel for the purification of carbonic anhydrases. Journal of Enzyme Inhibition and Medicinal Chemistry, 30:240–4, (2015).
13. Maren TH. A simplified micromethod for the determination of carbonic anhydrase and its inhibitors. Journal of Pharmacology and Experimental Therapeutics, 130:2629–34, (1960).
14. Jeziorska M, McCollum C, Wooley DE. Observations on bone formation and remodelling in advanced atherosclerotic lesions of human carotid arteries. Virchows Archiv., 433:559–65, (1998).
15. Detrano RC, Doherty TM, Davies MJ, Stary HC. Predicting coronary events with coronary calcium: pathophysiologic and clinical problems. Current Problems in Cardiology., 25: 374–40, (2000).
16. Stary HC. Natural history of calcium deposits in atherosclerosis progression and regression. Zeitschrift für Kardiologie., 89 Suppl 2:28–35, (2000).
17. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature., 423:337–42, (2003).
18. Riihonen R, Supuran CT, Parkkila S, Pastorekova S, Vaananen HK, Laitala-Leinonen T. Membrane-bound carbonic anhydrases in osteoclasts. Bone., 40:1021–31, (2007).
19. Yuan L, Wang M, Liu T, et al. Carbonic anhydrase 1-mediated calcification is associated with atherosclerosis, and methazolamide alleviates its pathogenesis. Frontiers in Pharmacology., 10:766, (2019).
20. Oksala N, Levula M, Pelto-Huikko M, et al. Carbonic anhydrases II and XII are up-regulated in osteoclast-like cells in advanced human atherosclerotic plaques – Tampere Vascular Study. Annals of Medicine, 42:360–70, (2010).
21. Ayari H, Bricca G. Microarray analysis reveals overexpression of IBSP in human carotid plaques. Advances in Medical Sciences, 57: 334H, (2012).
22. Ercüment ÖLMEZ. Antimuscarinic Drugs. Turkiye Klinikleri Journal of Internal Medical Sciences, 1(18):58-68, (2005).
23. 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 7.3: Management of symptomatic bradycardia and tachycardia. Circulation, 112:IV-67–77. 10.1161/CIRCULATIONAHA.104.480988, (2005).
24. Cooper BE. Review and update on inotropes and vasopressors. American Association of Critical-Care Nurses Advanced Critical Care, Jan-Mar;19(1):5-13; quiz 14-5, (2008).
25. Şentürk, M., Ekinci, D., Göksu, S., & Supuran, C. T. , Effects of dopaminergic compounds on carbonic anhydrase isozymes I, II, and VI. Journal of enzyme inhibition and medicinal chemistry, 27(3), 365-369, (2012).
26. Ruffolo RR Jr. The pharmacology of dobutamine. The American Journal of the Medical Sciences., 294(4):244-8, (1987).
27. Şentürk, Murat, et al. "In vitro inhibition of human carbonic anhydrase I and II isozymes with natural phenolic compounds." Chemical biology & drug design 77.6, 494-499, (2011).
28. Jin L, Abrahams JP, Skinner R, Petitou M, Pike RN, Carrell RW. The anticoagulant activation of antithrombin by heparin. Proceedings of the National Academy of Sciences, 94:14683–14688, (1997).
29. Klein W, Buchwald A, Hillis SE, Monrad S, Sanz G, Graham A, Turpie G, van der Meer J, Olaisson E, Undeland S, Ludwig K, for the FRIC Investigators. Comparison of low-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease: Fragmin in Unstable Coronary Artery Disease Study (FRIC). Circulation, 96:61–68, (1997).
30. Kay R, Wong KS, Yu YL, Chan YW, Tsoi TH, Ahuja AT, Chan FL, Fong KY, Law CB, Wong A, Woo J. Low-molecular-weight heparin for the treatment of acute ischemic stroke. The New England Journal of Medicine, 333:1588–1593, (1995).
31. Chistiakov DA, Ashwell KW, Orekhov AN, Bobryshev YV. "Innervation of the arterial wall and its modification in atherosclerosis". Autonomic Neuroscience. 193: 7–11, (2015).
32. Gokce B, Gençer N, Arslan O, Turkoğlu SA, Alper M, Köçkar F. Evaluation of ın vitro effects of some analgesic drugs on erythrocyte and recombinant carbonic anhydrase I and II. Journal of Enzyme Inhibition and Medicinal Chemistry, 27(1): 37–42, (2012).
33. Gencer N, Demir D, Sonmez F, Kucukislamoglu M. New coumarin derivatives as carbonic anhydrase inhibitors. Bioorganic and Medicinal Chemistry, 20:2811–2821, (2012).
34. Karatas MO, Alici B, Cakir U, Cetinkaya E, Demir D, Ergün A, Gencer N , Arslan O. Synthesis and carbonic anhydrase inhibitory properties of novel coumarin derivatives. Journal of Enzyme Inhibition and Medicinal Chemistry, 28(2): 322–327, (2013).