Effects of cilostazol on the peripheral nerve function and structure in STZ-induced diabetic rats.
We examined the effect of cilostazol (CZ), antiplatelet agent and potent vasoactive compound, which has an inhibitory effect on tissue phosphodiesterase, on peripheral nerve in streptozotocin-induced diabetic rats. Diabetic rats were fed for 12 weeks with a chow containing 0.01% or 0.03% CZ (w/w) and the results were compared with untreated diabetic rats. The 0.03% CZ treatment significantly improved motor nerve-conduction velocity and restored nerve Na+, K(+)-ATPase activity in diabetic rats without affecting body weight and glycated hemoglobin levels, but the effects of 0.01% CZ treatment did not reach statistical difference. Elevated sorbitol and reduced myo-inositol levels in diabetic nerve tissues were not influenced by CZ treatment. Structural analysis of the sural nerve demonstrated a partial but significant effect on decreased mean myelinated fiber area and atrophic changes of the axon in diabetic rats treated with 0.01% CZ. CZ treatment inhibited reduction of pericyte area of endoneurial microvessels in diabetic rats. Expansion of endoneurial microvessels and luminal area in relation to vascular area also tended to be inhibited by CZ treatment. Thus CZ treatment ameliorated, although not completely, functional and structural abnormalities in peripheral nerve of diabetic rats without effecting the polyol pathway. These results support the contention that vascular factors may play an important role in the etiology of experimental diabetic neuropathy and suggest that CZ may have a beneficial therapeutic effect on diabetic neuropathy.
Uehara
K
K
Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Japan.
Sugimoto
K
K
Wada
R
R
Yoshikawa
T
T
Marukawa
K
K
Yasuda
Y
Y
Kimura
Y
Y
Yagihashi
S
S
D000818:Animals; D000077407:Cilostazol; D015331:Cohort Studies; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D007294:Inositol / Q000032:analysis; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D017933:Peripheral Nervous System / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D012584:Sciatic Nerve / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013012:Sorbitol / Q000032:analysis; D013497:Sural Nerve / Q000098:blood supply / Q000187:drug effects / Q000648:ultrastructure; D013777:Tetrazoles / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D007294:Inositol; D013012:Sorbitol; D000254:Sodium-Potassium-Exchanging ATPase; D000077407:Cilostazol