Muharrem TOPAL, Diler US ALTAY, Elif ŞAHİN, Ahmet ALVER

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

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.

Anahtar Kelimeler:

Karbonik Anhidraz II, Glukoz 6 Fosfat Dehidrogenaz, Ciglitazone, PPAR γ, Anemi

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

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.

Keywords:

Carbonic Anhydrase II, Glucose 6 Phosphate Dehydrogenase, Ciglitazone, PPARγ, Anemia,

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