EFFECTS OF BERAPROST SODIUM, A PROSTACYCLIN ANALOG, ON TAIL-FLICK RESPONSE IN 2 MODELS OF DIABETIC-NEUROPATHY IN RATS AND ITS MECHANISM

The effects of beraprost sodium (BPS), a stable prostacyclin analogue, on the tail flick (TF) latency were investigated in streptozotocin-in duced (STZ;55mg/kg, i.p.) diabetic male Sprague-Dawley (SD) rats and i n spontaneously diabetic WBN/Kob rats. The SD rats were divided into 5 groups, i.e., (I) normal, (II) diabetic control, diabetic treated wit h (III) BPS (10 mu g/kg/day), (IV) BPS (30 mu g/kg/day), and (V) aldos e reductase inhibitor (ARI; epalrestat, 50mg/kg/day). The drugs were a dministered orally. At 12 weeks, TF latency was significantly longer i n untreated diabetic rats than in normal rats. After 4 weeks treatment , BPS significantly improved the abnormality in TF latency dose-depend ently. But ARI did not normalize the response. The 45 weeks male WBN/K ob rats were divided into 2 groups: diabetic control and diabetic trea ted with BPS at 30 mu g/kg/day, p.o., respectively. Untreated, age-mat ched wistar rats were served as the normal group. At 61 weeks, TF late ncy was significantly longer in control WBN/Kob rats than in normal wi star rats in time-dependent manner. After 16 weeks treatment, BPS sign ificantly normalized the prolongation in TF latency. In in vivo experi ments, BPS significantly increased the cyclic AMP (cAMP) content in sc iatic nerves from normal rats dose-dependently, In STZ-induced diabeti c rats, cAMP content in sciatic nerves were significantly reduced, and 4 weeks treatment of BPS significantly restored this reduced cAMP con tent. It was suggested that BPS may be effective on diabetic neuropath y by, at least in part maintenance of cAMP contents in the nerves.