An inhibition of urinary albumin excretion by protease inhibitor in streptozotocin-diabetic rats

Abstract

To evaluate the protecting effect of camostat mesylate, N,N-dimethylcarbamoylmethyl-p-(p-guanidinobenzoyloxy)phenylacetate methanesulfonate, one of the synthetic trypsin inhibitors, on diabetic nephropathy, urinary albumin excretion was measured in streptozotocin-induced (50 mg/kg, i.p.) diabetic rats treated with oral camostat mesylate for 12 weeks. The rats were divided into three groups: (1) nondiabetic control rats; (2) diabetic rats, and (3) diabetic rats received rat chow containing 0.1% camostat mesylate (PI rats). After induction of diabetes, the ratio of kidney weight to body weight and urinary albumin excretion (UAE) were significantly increased. However, the ratio of kidney weight to body weight in PI rats was significantly lower than that in diabetic rats, and UAE in PI rats was also significantly lower than that in diabetic rats at 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 diabetic and PI rats. These results suggest that camostat mesylate reduces the UAE probably through an inhibitory effect on initial diabetic renal hypertrophy and that camostat mesylate is available for diabetic nephropathy.