Investigation of the In vitro Effects of Sultamycillin, Cefdinir, Vancomycin Hydrochloride and Colistimethate Sodium Agents Used as Antibiotics on Enzyme Activity of Human Serum Paraoxonase-I

Paraoxonase (PON1; E.C.3.1.8.1) is synthesized in the liver and hydrolyzes its specific substrate, paraoxone. It is an enzyme from the group of A-esterases bound to high density lipoprotein (HDL). The aim of this study was to investigate the in vitro effects of sultamicillin, cefdinir, vancomycin hydrochloride and colistimethate sodium active substances on the PON1 enzyme activity in human serum. The PON1 enzyme from the human serum was purified using ammonium sulfate precipitation (in the range of 60-80%), ion exchange chromatography, and gel filtration chromatography techniques approximately 320,7 fold with 44,6% yield. The paraoxonase activity of the enzyme at 412 nm was investigated to investigate the inhibition effects of the active substances. Paraoxone was used as the substrate. Sultamycillin and vancomycin hydrochloride showed noncompetetive inhibition for the PON1 enzyme, whereas cefdinir showed a uncompetitive inhibition and colistimethate sodium showed a competitive inhibition effect. Ki values are determined for sultamycillin as 38.3 mM; for vancomycin hydrochloride as 5.08 mM; for cefdinir as 0.86 mM; and for colistimethate sodium as 17.01 µM. According to the results, it was determined that the most effective inhibitor colistimethate sodium (IC50: 13.59 µM) was found on the PON1 enzyme with 50% reduction in activity at very low concentration.