AN INHIBITION OF URINARY ALBUMIN EXCRETION BY PROTEASE INHIBITOR IN STREPTOZOTOCIN-DIABETIC RATS

To evaluate the protecting effect of camostat mesylate, amoylmethyl-p- (p-guanidinobenzoyloxy)phenylacetate methanesulfonate, one of the synt hetic trypsin inhibitors, on diabetic nephropathy, urinary albumin exc retion was measured in streptozotocin-induced (50 mg/kg, i.p.) diabeti c rats treated with oral camostat mesylate for 12 weeks. The rates wer e divided into three groups: (1) nondiabetic control rats; (2) diabeti c rats, and (3) diabetic rats received rat chow containing 0.1% camost at mesylate (PI rats). After induction of diabetes, the ratio of kidne y weight to body weight and urinary albumin excretion (UAE) were signi ficantly increased. However, the ratio of kidney weight to body weight in PI rats was significantly lower than that in diabetic rats, and UA E in PI rats was also significantly lower than that in diabetic rats a t 4, 8 and 12 weeks. Kidney tissue insulin-like growth factor I (IGF-I ) contents were significantly reduced in diabetic rats, and there were no significant differences in kidney tissue IGF-I contents between di abetic and PI rats. These results suggest that camostat mesylate reduc es the UAE probably through an inhibitory effect on initial diabetic r enal hypertrophy and that camostat mesylate is available for diabetic nephropathy.