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The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase

Year 2022, Volume: 11 Issue: 1, 105 - 111, 19.03.2022
https://doi.org/10.37989/gumussagbil.1001449

Abstract

Ciglitazone is a compound belonging to the thiazolidinedione (TZD) class and has hypoglycemic effects. Although ciglitazone is not used as a drug, it has been used as a template for the development of other TZD group drugs. Like many TZD group drugs, ciglitazone causes anemia. In this study, the effects of ciglitazone on the enzyme activities of Glucose-6- Phosphate Dehydrogenase (G6PD) and Carbonic Anhydrase II (CA II), which have important functions in maintaining erythrocyte functions and integrity, were investigated in vitro. Pure human erythrocyte CA II and G6PD enzymes were used for activity measurements. Both esterase and hydratase activities were measured for CA II. The result of activity measurements, it was observed that ciglitazone inhibited CA II (IC50 =0.0063 mM for hydratase activity, and IC50 =0.047 mM for esterase activity) and G6PD (IC50 = 0.067 mM) activities. As a result, it was concluded that these enzyme inhibitions may be important in the anemia-causing mechanisms of cigitazone.

References

  • 1. Lindskog, S. (1997).“Structure and Mechanism of Carbonic Anhydrase”. Pharmacol Ther, 74 (1), 1-20.
  • 2. Supuran, C.T. (2008).“Carbonic Anhydrases as Drug Targets”. Curr Pharm Des, 14 (7), 601-2.
  • 3. Zamanova, S, Shabana, A.M, Mondal, U.K. and Ilies, M.A. (2019). “Carbonic Anhydrases as Disease Markers”. Expert Opin Ther Pat, 29 (7), 509-533.
  • 4. Kuo, W.H, Yang, S.F, Hsieh, Y.S, Tsai, C.S, Hwang, W.L. and Chu, S.C. (2005). “Differential Expression of Carbonic Anhydrase Isoenzymes in Various Types of Anemia”. Clin Chim Act, 351 (1-2), 79-86.
  • 5. Mehta, A, Mason, P.J. and Vulliamy, T.J. (2000).“Glucose-6-Phosphate Dehydrogenase Deficiency”. Baillière's Best Practice & Research, Clinical Haematology, 13, 21-38.
  • 6. Stincone, A, Prigione, A, Cramer, T, Wamelink, M.M, Campbell, K, Cheung, E, Olin-Sandoval, V, Grüning, N.M, Krüger, A, Tauqeer Alam, M, Keller, M.A, Breitenbach, M, Brindle, K.M, Rabinowitz, J.D. and Ralser, M. (2015). “The Return of Metabolism: Biochemistry and Physiology of the Pentose Phosphate Pathway”. Biol Rev Camb Philos Soc, 290 (3), 927-63.
  • 7. Fiorelli, G, Montemuros, F. and Cappellini, M. (2000).“Chronic Non-Spherocytic Haemolytic Disorders Associated with G6PD Variants”. Baillière's Clinical Haematology, 13, 39-55.
  • 8. Mohanty, J.G, Nagababu, E. and Rifkind, J.M. (2014). “Red Blood Cell Oxidative Stress Impairs Oxygen Delivery and Induces Red Blood Cell Aging”. Front Physiol, 28, 5:84.
  • 9. Hulin, B, McCarthy, P.A. and Gibbs, E.M. (1996). “The Ciglitazone Family of Antidiabetic Agents.” Current Pharmaceutical Design, 2, 85–102.
  • 10. Kielian, T, Syed, M.M, Liu, S, Phulwani, N.K, Phillips, N, Wagoner, G, Drew, P.D. and Esen, N. (2008). “The Synthetic Peroxisome Proliferator-Activated Receptor-Gamma Agonist Ciglitazone Attenuates Neuroinflammation and Accelerates Encapsulation in Bacterial Brain Abscesses”. J Immunol, 180 (7), 5004-16.
  • 11. Sen, U, Rodriguez, W.E, Tyagi, N, Kumar, M, Kundu, S. and Tyagi, S.C. (2008). “Ciglitazone, a Ppargamma Agonist, Ameliorates Diabetic Nephropathy in Part Through Homocysteine Clearance”. Am J Physiol Endocrinol Metab, 295 (5), E1205-12.
  • 12. Schoonjans, K. and Auwerx, J. (2000). “Thiazolidinediones: an Update”. Lancet, 355 (9208), 1008-10.
  • 13. Saad, M.F, Greco, S, Osei, K, Lewin, A.J, Edwards, C, Nunez, M. and Reinhardt, R.R. (2004). “Ragaglitazar Dose-Ranging Study Group. Ragaglitazar İmproves Glycemic Control and Lipid Profile in Type 2 Diabetic Subjects: A 12-Week, Double-Blind, Placebo-Controlled Dose-Ranging Study with an Open Pioglitazone Arm”. Diabetes Care, 27 (6), 1324-9.
  • 14. Nieomoeller, O.M, Mahmud, H, Föller, M, Wieder, T. and Lang, F. (2008). “Ciglitazone and 15d-PGJ2 Induced Suicidal Erythrocyte Death”. Cellular Physiology and biochemistry, 22, 237-244.
  • 15. Cho, H. and Tai, H.H. (2002). “Inhibition of NAD+-dependent 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) by Cyclooxygenase Inhibitors and Chemopreventive Agents”. Prostaglandins Leukot Essent Fatty Acids, 67 (6), 461-5.
  • 16. Arlt, W, Auchus, R.J. and Miller, W.L. (2001).“Thiazolidinediones But Not Metformin Directly Inhibit The Steroidogenic Enzymes P450c17 and 3-Beta-Hydroxysteroid Dehydrogenase”. J Biol Chem, 276 (20), 16767-71.
  • 17. Wilbur, K.M. and Anderson, N.G. (1948). “Electrometric and Colorimetric Determination of Carbonic Anhydrase”. Journal of Biological Chemistry, 76, 146.
  • 18. Armstrong, J.M, Myers, D.V, Verpoorte, J.A. and Edsall, J.T. (1966). “Purification and Properties of Human Erythrocyte Carbonic Anhydrase”. J. Biol. Chem, 214, 513.
  • 19. Beutler, E. (1971). “Red Cell Metabolism Manual of Biochemical Methods”. London Academic Press, 68–70
  • 20. Viljoen, A. and Sinclair, A. (2009). “Safety and Efficacy of Rosiglitazone in The Elderly Diabetic Patient”. Vascular Health and Risk Management, 5, 389-395.
  • 21. Blicklé, J.F. (2001). “Thiazolidinediones: Clinical Data and Perspectives”. Diabetes Metab, 27, 279-85.
  • 22. Kuhn, V, Diederich, L, Keller, T.C.S, Kramer, C.M, Lückstädt, W, Panknin, C, Suvorava, T, Isakson, B.E, Kelm, M. and Cortese-Krott, M.M. (2017). “Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia”. Antioxid Redox Signal, 26 (13), 718-742.
  • 23. Careter, M.J. (1972). “Carbonic Anhydrase: Isoenzymes Properties, Distrubition and Functional Significore”. Biological Review, 42, 462-475.
  • 24. Geers, C. and Gros, G. (2000). “Carbon Dioxide Transport and Carbonic Anhydrase in Blood and Muscle”. Physiol Rev, 80 (2), 681-715.
  • 25. Pastarekova, S, Parkkıla, S, Pastorek, J. and Supuran, T.C. (2004). “Carbonic Anhydrases: Current State of the Art, Therapeutic Applications and Future Prospects”. Journal of Enzyme Inhibition and Medicinal Chemistry, 19, 199-229.
  • 26. Wang, Y.P, Zhou, L.S, Zhao, Y.Z, Wang, S.W, Chen, L.L, Liu, L.X, Ling, Z.Q, Hu, F.J, Sun, Y.P, Zhang, J.Y, Yang, C, Yang, Y, Xiong, Y, Guan, K. and Ye, D. (2014). “Regulation of G6PD Acetylation by SIRT2 and KAT9 Modulates NADPH Homeostasis and Cell Survival During Oxidative Stress”. EMBO J, 33 (12), 1304-20.
  • 27. Peters, A.L. and Van Noorden, C.J. (2009).“Glucose-6-Phosphate Dehydrogenase Deficiency and Malaria: Cytochemical Detection of Heterozygous G6PD Deficiency in Women.” J Histochem Cytochem, 57 (11), 1003-11.

Ciglitazonun Karbonik Anhidraz II ve Glukoz-6-Fosfat Dehidrogenaz Enzim Aktiviteleri Üzerine Etkileri

Year 2022, Volume: 11 Issue: 1, 105 - 111, 19.03.2022
https://doi.org/10.37989/gumussagbil.1001449

Abstract

Ciglitazone thiazolidinedione (TZD) sınıfına ait bir bileşiktir ve hipoglisemik etkilere sahiptir. Ciglitazone bir ilaç olarak kullanılmamasına rağmen, diğer TZD grubu ilaçların gelişmesi için bir kalıp olarak kullanılmıştır. Pek çok TZD grubu ilaç gibi ciglitazone da anemiye sebep olmaktadır. Bu çalışmada eritrosit fonksiyonlarının ve bütünlüğünün sürdürülmesinde önemli fonksiyonlara sahip olan Glukoz-6-Fosfat Dehidrogenaz (G6PD) ve Karbonik Anhidraz II (CA II) enzim aktiviteleri üzerine ciglitazonun etkileri in vitro olarak incelendi. Aktivite ölçümlerini için saf insan eritrosit CA II ve G6PD enzimleri kullanıldı. CAII için hem esteraz hem de hidrataz aktiviteleri ölçüldü. Aktivite ölçümleri sonucunda, ciglitazone’un CA II aktivitesini (hidrataz aktivitesi için IC50 =0.0063 mM ve esteraz aktivitesi için IC50 =0.047 mM) ve G6PD (IC50= 0.067 mM) aktivitesini inhibe ettiği gözlendi. Sonuç olarak bu enzim inhibisyonlarının, ciglitazone’un anemi oluşturma mekanizmalarında önemli olabileceği kanaatine varıldı.

References

  • 1. Lindskog, S. (1997).“Structure and Mechanism of Carbonic Anhydrase”. Pharmacol Ther, 74 (1), 1-20.
  • 2. Supuran, C.T. (2008).“Carbonic Anhydrases as Drug Targets”. Curr Pharm Des, 14 (7), 601-2.
  • 3. Zamanova, S, Shabana, A.M, Mondal, U.K. and Ilies, M.A. (2019). “Carbonic Anhydrases as Disease Markers”. Expert Opin Ther Pat, 29 (7), 509-533.
  • 4. Kuo, W.H, Yang, S.F, Hsieh, Y.S, Tsai, C.S, Hwang, W.L. and Chu, S.C. (2005). “Differential Expression of Carbonic Anhydrase Isoenzymes in Various Types of Anemia”. Clin Chim Act, 351 (1-2), 79-86.
  • 5. Mehta, A, Mason, P.J. and Vulliamy, T.J. (2000).“Glucose-6-Phosphate Dehydrogenase Deficiency”. Baillière's Best Practice & Research, Clinical Haematology, 13, 21-38.
  • 6. Stincone, A, Prigione, A, Cramer, T, Wamelink, M.M, Campbell, K, Cheung, E, Olin-Sandoval, V, Grüning, N.M, Krüger, A, Tauqeer Alam, M, Keller, M.A, Breitenbach, M, Brindle, K.M, Rabinowitz, J.D. and Ralser, M. (2015). “The Return of Metabolism: Biochemistry and Physiology of the Pentose Phosphate Pathway”. Biol Rev Camb Philos Soc, 290 (3), 927-63.
  • 7. Fiorelli, G, Montemuros, F. and Cappellini, M. (2000).“Chronic Non-Spherocytic Haemolytic Disorders Associated with G6PD Variants”. Baillière's Clinical Haematology, 13, 39-55.
  • 8. Mohanty, J.G, Nagababu, E. and Rifkind, J.M. (2014). “Red Blood Cell Oxidative Stress Impairs Oxygen Delivery and Induces Red Blood Cell Aging”. Front Physiol, 28, 5:84.
  • 9. Hulin, B, McCarthy, P.A. and Gibbs, E.M. (1996). “The Ciglitazone Family of Antidiabetic Agents.” Current Pharmaceutical Design, 2, 85–102.
  • 10. Kielian, T, Syed, M.M, Liu, S, Phulwani, N.K, Phillips, N, Wagoner, G, Drew, P.D. and Esen, N. (2008). “The Synthetic Peroxisome Proliferator-Activated Receptor-Gamma Agonist Ciglitazone Attenuates Neuroinflammation and Accelerates Encapsulation in Bacterial Brain Abscesses”. J Immunol, 180 (7), 5004-16.
  • 11. Sen, U, Rodriguez, W.E, Tyagi, N, Kumar, M, Kundu, S. and Tyagi, S.C. (2008). “Ciglitazone, a Ppargamma Agonist, Ameliorates Diabetic Nephropathy in Part Through Homocysteine Clearance”. Am J Physiol Endocrinol Metab, 295 (5), E1205-12.
  • 12. Schoonjans, K. and Auwerx, J. (2000). “Thiazolidinediones: an Update”. Lancet, 355 (9208), 1008-10.
  • 13. Saad, M.F, Greco, S, Osei, K, Lewin, A.J, Edwards, C, Nunez, M. and Reinhardt, R.R. (2004). “Ragaglitazar Dose-Ranging Study Group. Ragaglitazar İmproves Glycemic Control and Lipid Profile in Type 2 Diabetic Subjects: A 12-Week, Double-Blind, Placebo-Controlled Dose-Ranging Study with an Open Pioglitazone Arm”. Diabetes Care, 27 (6), 1324-9.
  • 14. Nieomoeller, O.M, Mahmud, H, Föller, M, Wieder, T. and Lang, F. (2008). “Ciglitazone and 15d-PGJ2 Induced Suicidal Erythrocyte Death”. Cellular Physiology and biochemistry, 22, 237-244.
  • 15. Cho, H. and Tai, H.H. (2002). “Inhibition of NAD+-dependent 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) by Cyclooxygenase Inhibitors and Chemopreventive Agents”. Prostaglandins Leukot Essent Fatty Acids, 67 (6), 461-5.
  • 16. Arlt, W, Auchus, R.J. and Miller, W.L. (2001).“Thiazolidinediones But Not Metformin Directly Inhibit The Steroidogenic Enzymes P450c17 and 3-Beta-Hydroxysteroid Dehydrogenase”. J Biol Chem, 276 (20), 16767-71.
  • 17. Wilbur, K.M. and Anderson, N.G. (1948). “Electrometric and Colorimetric Determination of Carbonic Anhydrase”. Journal of Biological Chemistry, 76, 146.
  • 18. Armstrong, J.M, Myers, D.V, Verpoorte, J.A. and Edsall, J.T. (1966). “Purification and Properties of Human Erythrocyte Carbonic Anhydrase”. J. Biol. Chem, 214, 513.
  • 19. Beutler, E. (1971). “Red Cell Metabolism Manual of Biochemical Methods”. London Academic Press, 68–70
  • 20. Viljoen, A. and Sinclair, A. (2009). “Safety and Efficacy of Rosiglitazone in The Elderly Diabetic Patient”. Vascular Health and Risk Management, 5, 389-395.
  • 21. Blicklé, J.F. (2001). “Thiazolidinediones: Clinical Data and Perspectives”. Diabetes Metab, 27, 279-85.
  • 22. Kuhn, V, Diederich, L, Keller, T.C.S, Kramer, C.M, Lückstädt, W, Panknin, C, Suvorava, T, Isakson, B.E, Kelm, M. and Cortese-Krott, M.M. (2017). “Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia”. Antioxid Redox Signal, 26 (13), 718-742.
  • 23. Careter, M.J. (1972). “Carbonic Anhydrase: Isoenzymes Properties, Distrubition and Functional Significore”. Biological Review, 42, 462-475.
  • 24. Geers, C. and Gros, G. (2000). “Carbon Dioxide Transport and Carbonic Anhydrase in Blood and Muscle”. Physiol Rev, 80 (2), 681-715.
  • 25. Pastarekova, S, Parkkıla, S, Pastorek, J. and Supuran, T.C. (2004). “Carbonic Anhydrases: Current State of the Art, Therapeutic Applications and Future Prospects”. Journal of Enzyme Inhibition and Medicinal Chemistry, 19, 199-229.
  • 26. Wang, Y.P, Zhou, L.S, Zhao, Y.Z, Wang, S.W, Chen, L.L, Liu, L.X, Ling, Z.Q, Hu, F.J, Sun, Y.P, Zhang, J.Y, Yang, C, Yang, Y, Xiong, Y, Guan, K. and Ye, D. (2014). “Regulation of G6PD Acetylation by SIRT2 and KAT9 Modulates NADPH Homeostasis and Cell Survival During Oxidative Stress”. EMBO J, 33 (12), 1304-20.
  • 27. Peters, A.L. and Van Noorden, C.J. (2009).“Glucose-6-Phosphate Dehydrogenase Deficiency and Malaria: Cytochemical Detection of Heterozygous G6PD Deficiency in Women.” J Histochem Cytochem, 57 (11), 1003-11.
There are 27 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Original Article
Authors

Muharrem Topal This is me

Diler Us Altay 0000-0002-0465-8403

Elif Şahin 0000-0001-5864-9548

Ahmet Alver 0000-0002-9617-6689

Publication Date March 19, 2022
Published in Issue Year 2022 Volume: 11 Issue: 1

Cite

APA Topal, M., Us Altay, D., Şahin, E., Alver, A. (2022). The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi, 11(1), 105-111. https://doi.org/10.37989/gumussagbil.1001449
AMA Topal M, Us Altay D, Şahin E, Alver A. The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi. March 2022;11(1):105-111. doi:10.37989/gumussagbil.1001449
Chicago Topal, Muharrem, Diler Us Altay, Elif Şahin, and Ahmet Alver. “The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase”. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 11, no. 1 (March 2022): 105-11. https://doi.org/10.37989/gumussagbil.1001449.
EndNote Topal M, Us Altay D, Şahin E, Alver A (March 1, 2022) The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 11 1 105–111.
IEEE M. Topal, D. Us Altay, E. Şahin, and A. Alver, “The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase”, Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi, vol. 11, no. 1, pp. 105–111, 2022, doi: 10.37989/gumussagbil.1001449.
ISNAD Topal, Muharrem et al. “The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase”. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 11/1 (March 2022), 105-111. https://doi.org/10.37989/gumussagbil.1001449.
JAMA Topal M, Us Altay D, Şahin E, Alver A. The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi. 2022;11:105–111.
MLA Topal, Muharrem et al. “The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase”. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi, vol. 11, no. 1, 2022, pp. 105-11, doi:10.37989/gumussagbil.1001449.
Vancouver Topal M, Us Altay D, Şahin E, Alver A. The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi. 2022;11(1):105-11.