Anti-diabetic Properties of Calcium Channel Blockers: Inhibition Effects on Aldose Reductase Enzyme Activity

Abstract

Aldose reductase (AR) belongs to NADPH-dependent oxidoreductases and converts glucose to sorbitol in the polyol pathway. AR inhibition is essential to prevent diabetic complications. Here, AR was purified from sheep kidney using simple methods and determined the interactions between some calcium channel blockers and the enzyme. It was found that calcium channel blockers (cinnarizine, nilvadipine, amlodipine besylate, nifedipine, isradipine, and nitrendipine) exhibit potential inhibitor properties for sheep kidney AR with IC50 values in the range of 5.87-8.77 mu M and K-i constants in the range of 2.07 +/- 0.72-5.62 +/- 1.53 mu M. The calcium channel blockers showed different inhibition mechanisms. It was determined that all studied compounds showed competitive inhibition effect except for isradipine and nitrendipine. They showed non-competitive inhibition. Among these drugs, cinnarizine was found to be the most potent AR inhibitor (K-i: 2.07 +/- 0.72 mu M). They may be useful in the treatment and/or prevention of diabetic complications.