Effects of some antibiotics on enzyme activities of carbonic anhydrase from erythrocytes in vivo and in vitro

Abstract

In this study, firstly, the effects of eight antibiotics namely, chlarithromycin, chloramphenicol, rifamycin SV, clindamycin phosphate, ciprofloxacin, gentamycin sulfate, sodium ampicillin and cefazolin sodium, on human carbonic anhydrase (hCA) (EC 4.2.1.1.) isozymes have been investigated in vitro. Human erythrocytes CA-I and CA-II isozymes were separately purified by affinity chromatography. Inhibition effects of eight different antibiotics on hCA isozymes were determined using the $CO _2$ hydratase method by plotting activity % vs [medical drug].$IC _{50}$ values of the antibiotics exhibiting inhibition effects were found by means of these graphs. It was observed that each antibiotics showed an inhibition effect on hCA-I and hCA-II hydratase activity. Sodium ampicillin showed greatest inhibition effect on hCA-I and hCA-II activity from in vitro studies. In order to determine the inhibition statue of these drugs on a living system, the effects of same antibiotics on CA enzyme activity of mouse erythrocytes was investigated in vivo. Ciprofloxacin (3.2 mg/kg), chlarithromycin (7.14 mg/kg), rifamycin SV (3.56 mg/kg) lead to the significant increase in mouse erthrocytes CA (mCA) after 4 h drug administration. As well gentamycin sulfate (3.2 mg/kg) and sodium ampicillin (17.12 mg/kg) after 2 h and clindamycin phosphate (2.143 mg/kg) after 2 h and 6 h drug administration, lead to increase in mCA. Chloramphenicol (12.5 mg/kg) did not exhibit any effect for the mCA, in vivo. However, CA activity after sodium ampicillin and cefazolin sodium administration showed statistically significant decrease at 4 h of drug administration in vivo (p: 0.014 and 0.016, respectively).