Bülent ŞENGÜL, Mehmet Mustafa İŞGÖR, Namık KILINÇ, Zuhal ALIM, Şükrü BEYDEMİR

İnsan Eritrosit Karbonik Anhidraz İzoenzimleri Üzerine Bazı Kardiyovasküler Terapötiklerin İnhibisyon Etkilerinin İncelenmesi

Karbonik anhidraz enzimi, asit-baz düzenlemesi ve solunum gibi metabolik olaylarda hayati rol oynar. Bu çalışmada, bazı kardiyovasküler terapötiklerin (esmolol hidroklorür, amiodaron hidroklorür, lidokain hidroklorür) insan eritrositleri karbonik anhidraz I ve II izoenzimleri (hCA-I ve hCA-II) aktiviteleri üzerine inhibisyon etkilerinin belirlenmesi amaçlanmıştır. Bu amaçla, insan eritrositlerinden afinite kromatografisi yardımıyla karbonik anhidraz izoenzimleri (CA-I ve CA-II) saflaştırıldı. Enzim saflıkları SDS-PAGE ile kontrol edildi. Saflaştırmadan sonra, kardiyovasküler terapötiklerin hCA-I ve hCA-II aktivitesi üzerindeki inhibitör etkileri, in vitro olarak esteraz yöntemi kullanılarak farklı ilaç konsantrasyonlarında belirlendi. Üç kardiyovasküler terapötik doza bağımlı olarak enzim aktivitelerini azalttı. Amiodaron hidroklorür, esmolol hidroklorür ve lidokain hidroklorür’ün IC50 değerleri hCA-I için sırasıyla 0.91 mM, 5 mM, 5.8 mM olarak, hCA-II için sırasıyla 0.41 mM, 3.5 mM, 6.36 mM olarak bulundu. Bulgularımız, kardiyovasküler terapötiklerin in vitro koşullarda hCA-I ve hCAII aktivitesini önemli ölçüde inhibe ettiğini göstermektedir. Bu nedenle, bu ilaçların kontrolsüz kullanımı insan sağlığı için ciddi yan etkilere neden olabilir.

Evaluation of Inhibition Effects of Some Cardiovascular Therapeutics on Human Erythrocyte Carbonic Anhydrase Isoenzymes

Carbonic anhydrase enzyme plays a vital role in metabolic events such as acid-base regulation and respiration. Inour research, it is tried to determine the inhibitory influences of the cardiovascular therapeutics esmololhydrochloride, amiodarone hydrochloride and lidocaine hydrochloride on human erythrocytes carbonic anhydrases(hCA I and II). In accordance with this purpose, carbonic anhydrase isoenzymes were purified from humanerythrocytes by using affinity chromatography method. Enzyme purity was checked by SDS-PAGEelectrophoresis method. After the carbonic anhydrase enzymes were purified, the inhibitory affects ofcardiovascular therapeutics on these enzymes, using esterase activity, which is the method of measuring in vitroactivity, were examined. The three cardiovascular therapeutics dose-dependently decreased activity of hCAs. IC50values of amiodarone hydrochloride, esmolol hydrochloride and lidocaine hydrochloride were found to be,respectively, 0.91 mM, 5 mM, 5.8 mM for hCA-I and 0.41 mM, 3.5 mM, and 6.36 mM for hCA-II. Our resultsproved that, under in vitro conditions, cardiovascular therapeutics significantly inhibit human CA-I and IIactivities. So, irregular use of these medicines may cause serious adverse effects in terms of human health.

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