EFFECT OF AN ALDOSE REDUCTASE INHIBITOR ON GLOMERULAR-BASEMENT-MEMBRANE ANIONIC SITES IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

The present study was conducted in order to determine whether an aldos e reductase inhibitor (ARI), epalrestat, prevents the progression of d iabetic nephropathy in rats. Rats were made diabetic by intravenous in jection of streptozotocin (STZ 50 mg/kg) and epalrestat (100 mg/kg) wa s administered orally through a gastric tube once daily for 4 weeks. E xamination by electron microscope revealed that the number of anionic sites (AS) in the lamina rara externa per 1000 nm of glomerular baseme nt membrane (GBM) was significantly decreased in diabetic rats compare d to control values (17.6 +/- 0.4 vs. 21.9 +/- 0.4, P < 0.01), whereas , significant recovery(20.3 +/- 0.7, P < 0.05) was observed after 4 we eks of epalrestat treatment. Urinary albumin excretion (UAE) rate was markedly increased in diabetic rats and the treatment resulted in its significant suppression from diabetic rats. In conclusion, administrat ion of epalrestat to diabetic rats is capable of preventing a reductio n in the number of AS in GBM which would ameliorate an increased perme ability of the basement membrane leading to albuminuria.