ABSTRACT
The aim of this study was to investigate the inhibitory effects of some pesticides known to have harmful effects on human health on carbonic anhydrase isoenzymes. Therefore, carbonic anhydrase isoenzymes (hCA I and II) were purified from human erythrocytes. The isoenzymes were purified from human erythrocytes by using an affinity column that has the chemical structure of Sepharose-4B-4-(6-amino-hexyloxy)-benzenesulfonamide. The purity of the isoenzymes was checked by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDSPAGE). It was determined that the pesticides used in this study inhibit hCA I and hCA II isoenzymes at different levels in vitro. It was determined that the strongest inhibitor for the hCA I enzyme was Carbofuran (IC50 :6.52 µM; Ki : 3.58 µM) and the weakest one was 1-Naphtol (IC50 :16.55 µM; Ki : 14.4 µM) among these pesticides. It was also found that the strongest inhibitor for the hCA II enzyme was coumatetralil (IC50 :5.06 µM; Ki : 1.62 µM) and the weakest one was Dimethachlor (IC50 14.6 µM; Ki : 8.44 µM).
Subject(s)
Carbonic Anhydrases , Pesticides , Humans , Carbonic Anhydrase Inhibitors/pharmacology , Carbonic Anhydrase Inhibitors/chemistry , Isoenzymes/chemistry , Isoenzymes/metabolism , Carbonic Anhydrase I/chemistry , Carbonic Anhydrase I/metabolism , Carbonic Anhydrase II/chemistry , Carbonic Anhydrase II/metabolism , Pesticides/pharmacology , Erythrocytes , Structure-Activity RelationshipABSTRACT
Cardiovascular diseases are the leading cause of mortality worldwide. In recent years, the relationship between carbonic anhydrase inhibitors and atherosclerosis has attracted attention. In this study, we aimed to determine the in vitro effects of 35 frequently used cardiac drugs on human carbonic anhydrase I (hCA I) and II (hCA II). The inhibitory effects of the drugs on hCA I and hCA II were determined with both the hydratase and esterase methods. The most potent inhibitors observed were propafenone (hCA I: 2.8 µM and hCA II: 3.02 µM) and captopril (hCA I: 1.58 µM and hCA II: 6.25 µM). Isosorbide mononitrate, propranolol, furosemide, and atorvastatin were also potent inhibitors. The inhibitor constant, Ki, value from the Lineweaver-Burk plot for propafenone was 2.38 µM for hCA I and 2.97 µM for hCA II. The tested cardiac drugs showed potent in vitro inhibition of the hCA I and II isozymes. Especially, in patients with atherosclerotic heart disease, these drugs may be preferred primarily due to the beneficial effects of carbonic anhydrase inhibition on atherosclerosis.