The interactions of cephalosporins on polyol pathway enzymes from sheep kidney

Abstract

Context: Cephalosporins are derived from the fungus Acremonium. Due to their strong bactericidal ability, these drugs have to a wide usage in medicine.Objective: An investigation of the effects on sheep renal aldose reductase (AR) and sorbitol dehydrogenase (SDH) of cefoperazone, cefazolin, cefuroxime, ceftazidime and ceftriaxone as cephalosporin drugs was carried out in the present study. Methods: AR and SDH were purified from sheep kidney by ion exchange, gel filtration and affinity methods with approximately 219- and 484-fold, respectively. Some kinetic properties of the enzymes were determined such as optimal pH, optimal ionic strength, optimal temperature, stable pH, K-m and V-max. IC50 values of the drugs were found for each enzyme. Results: While the AR was inhibited by all drugs, SDH enzyme was inhibited by only CXM (IC50 8.10mM). Interestingly, CZO activated SDH enzyme. This result was evaluated as important for the flow of the polyol reactions. K-i values and inhibition types were determined for AR. However, these values could not have determined for SDH, due to insufficient inhibition. Conclusions: From these results, it was concluded that cephalosporins may have an important effect on flow of the polyol metabolism.