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

Yıl 2022, Cilt 11, Sayı 1, 105 - 111, 19.03.2022
https://doi.org/10.37989/gumussagbil.1001449

Öz

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.

Kaynakça

  • 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.

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

Yıl 2022, Cilt 11, Sayı 1, 105 - 111, 19.03.2022
https://doi.org/10.37989/gumussagbil.1001449

Öz

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.

Kaynakça

  • 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.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Bilimleri ve Hizmetleri
Bölüm Araştırma Makaleleri
Yazarlar

Muharrem TOPAL Bu kişi benim
KARADENİZ TEKNİK ÜNİVERSİTESİ, TIP FAKÜLTESİ
0000-0001-2345-6789
Türkiye


Diler US ALTAY
ORDU ÜNİVERSİTESİ, SAĞLIK BİLİMLERİ FAKÜLTESİ
0000-0002-0465-8403
Türkiye


Elif ŞAHİN
KARADENİZ TEKNİK ÜNİVERSİTESİ, TIP FAKÜLTESİ
0000-0001-5864-9548
Türkiye


Ahmet ALVER (Sorumlu Yazar)
KARADENİZ TEKNİK ÜNİVERSİTESİ, TIP FAKÜLTESİ
0000-0002-9617-6689
Türkiye

Yayımlanma Tarihi 19 Mart 2022
Yayınlandığı Sayı Yıl 2022, Cilt 11, Sayı 1

Kaynak Göster

Bibtex @araştırma makalesi { gumussagbil1001449, journal = {Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi}, issn = {}, eissn = {2146-9954}, address = {}, publisher = {Gümüşhane Üniversitesi}, year = {2022}, volume = {11}, pages = {105 - 111}, doi = {10.37989/gumussagbil.1001449}, title = {The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase}, key = {cite}, author = {Topal, Muharrem and Us Altay, Diler and Şahin, Elif and Alver, Ahmet} }
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 . DOI: 10.37989/gumussagbil.1001449
MLA 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 11 (2022 ): 105-111 <https://dergipark.org.tr/tr/pub/gumussagbil/issue/68960/1001449>
Chicago 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 11 (2022 ): 105-111
RIS TY - JOUR T1 - The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase AU - Muharrem Topal , Diler Us Altay , Elif Şahin , Ahmet Alver Y1 - 2022 PY - 2022 N1 - doi: 10.37989/gumussagbil.1001449 DO - 10.37989/gumussagbil.1001449 T2 - Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi JF - Journal JO - JOR SP - 105 EP - 111 VL - 11 IS - 1 SN - -2146-9954 M3 - doi: 10.37989/gumussagbil.1001449 UR - https://doi.org/10.37989/gumussagbil.1001449 Y2 - 2022 ER -
EndNote %0 Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase %A Muharrem Topal , Diler Us Altay , Elif Şahin , Ahmet Alver %T The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase %D 2022 %J Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi %P -2146-9954 %V 11 %N 1 %R doi: 10.37989/gumussagbil.1001449 %U 10.37989/gumussagbil.1001449
ISNAD Topal, Muharrem , Us Altay, Diler , Şahin, Elif , Alver, Ahmet . "The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase". Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 11 / 1 (Mart 2022): 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. 2022; 11(1): 105-111.
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): 105-111.
IEEE M. Topal , D. Us Altay , E. Şahin ve A. Alver , "The Effects of Ciglitazone on Enzyme Activities of Carbonic Anhydrase II and Glucose-6- Phosphate Dehydrogenase", Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi, c. 11, sayı. 1, ss. 105-111, Mar. 2022, doi:10.37989/gumussagbil.1001449