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 vasodilating agent, to prevent functional, structural and biochemical abnormalities including delayed motor nerve conduction velocity (MNCV), morphological changes in myelinated fibers, and decreased Na(+)-K(+) -ATPase activity in the peripheral nerves of rats with streptozotocin (STZ)-induced diabetes. Cilostazol treatment (30 mg/kg/day p.o.) for 10 weeks significantly prevented the delay in MNCV in the tail nerve, and morphometric analysis of the sural nerves revealed that this dose of cilostazol had a significant effect on reduction of average size of myelinated fibers. In untreated diabetic rats, cyclic AMP content and Na(+)-K(+)-ATPase 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 treatment of diabetic neuropathy, possibly via improvement of nerve Na(+)-K(+) -ATPase activity and cyclic AMP content. Cilostazol may thus be a potent drug for the clinical treatment of diabetic neuropathy.
Naka
K
K
The First Department of Medicine, Wakayama University of Medical Science, Wakayama, Japan.
Sasaki
H
H
Kishi
Y
Y
Furuta
M
M
Sanke
T
T
Nanjo
K
K
Mukoyama
M
M
D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D000077407:Cilostazol; D000242:Cyclic AMP / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology* / Q000517:prevention & control; D005343:Fibrinolytic Agents / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism; D013497:Sural Nerve / Q000187:drug effects / Q000502:physiology; D013623:Tail / Q000294:innervation; D013777:Tetrazoles / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D013979:Tibial Nerve / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use
D001786:Blood Glucose; D005343:Fibrinolytic Agents; D013777:Tetrazoles; D014665:Vasodilator Agents; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D000077407:Cilostazol