Inhibition studies on chicken muscle aldose reductase

Several compounds that are known to inhibit mammalian aldose reductases were examined for their effects on chicken muscle aldose reductase (EC 1.1.1.21). Sorbinil was the most effective compound tested. Alrestatin and phenobarbital were effective inhibitors of the enzyme although their IC50 values were 10-fold more than that of Sorbinil. Indomethacin, diphenylhydantoin, phenacetin, and valproate were also inhibitors of chicken muscle aldose reductase but were less effective. These compounds are all non-competitive inhibitors with respect to substrate. Menadione bisulfite, a watersoluble analog of Vitamin K3 which is a substrate for carbonyl reductase but not aldose reductase, was a competitive inhibitor of chicken aldose reductase with respect to substrate. This observation is discussed with reference to the possible treatment of muscular dystrophy with specific inhibitor of aldose reductases.