EFFECTS OF CILOSTAZOL ON DEVELOPMENT OF EXPERIMENTAL DIABETIC NEUROPATHY - FUNCTIONAL AND STRUCTURAL STUDIES, AND NA-K+-ATPASE ACIDITY IN PERIPHERAL-NERVE IN RATS WITH STREPTOZOTOCIN-INDUCED DIABETES()

We studied the ability of cilostazol (CL), an antithrombotic and vasod ilating agent, to prevent functional, structural and biochemical abnor malities including delayed motor nerve conduction velocity (MNCV), mor phological changes in myelinated fibers, and decreased Na+-K+-ATPase a ctivity in the peripheral nerves of rats with streptozotocin (STZ)-ind uced diabetes. Cilostazol treatment (30 mg/kg/day p.o.) for 10 weeks s ignificantly prevented the delay in MNCV in the tail nerve, and morpho metric analysis of the sural nerves revealed that this dose of cilosta zol had a significant effect on reduction of average size of myelinate d fibers. In untreated diabetic rats, cyclic AMP content and Na+-K+-AT Pase activity of peripheral nerve were each significantly less than in normal control rats. Cilostazol (30 mg/kg/day) prevented reduction of Na+-K+-ATPase activity. Decrease in cyclic AMP content was completely prevented with both doses of cilostazol (30 and 10 mg/kg/day). These findings suggest that cilostazol may have beneficial effects in the tr eatment of diabetic neuropathy, possibly via improvement of nerve Na+- K+-ATPase activity and cyclic AMP content. Cilostazol may thus be a po tent drug for the clinical treatment of diabetic neuropathy.