title: Effect of an aldose reductase inhibitor on glomerular basement membrane anionic sites in streptozotocin-induced diabetic rats.
abstract: The present study was conducted in order to determine whether an aldose reductase inhibitor (ARI), epalrestat, prevents the progression of diabetic nephropathy in rats. Rats were made diabetic by intravenous injection of streptozotocin (STZ 50 mg/kg) and epalrestat (100 mg/kg) was administered orally through a gastric tube once daily for 4 weeks. Examination by electron microscope revealed that the number of anionic sites (AS) in the lamina rara externa per 1000 nm of glomerular basement membrane (GBM) was significantly decreased in diabetic rats compared to control values (17.6 + or - 0.4 vs. 21.9 + or -0.4, P < 0.01), whereas, significant recovery (20.3 + or - 0.7, P < 0.05) was observed after 4 weeks 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, administration of epalrestat to diabetic rats is capable of preventing a reduction in the number of AS in GBM which would ameliorate an increased permeability of the basement membrane leading to albuminuria.
authors.affiliation: The Second Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Isogai
authors.forename: T
authors.initials: T
authors.lastname: Inokuchi
authors.forename: K
authors.initials: K
authors.lastname: Ohe
mesh_terms: D000284:Administration, Oral; D000419:Albuminuria / Q000378:metabolism; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D000838:Anions / Q000378:metabolism; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015331:Cohort Studies; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012236:Rhodanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013012:Sorbitol / Q000097:blood / Q000378:metabolism; D053778:Thiazolidines; D013997:Time Factors
chemical_list: D000838:Anions; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D053778:Thiazolidines; C038131:epalrestat; D013012:Sorbitol; D012236:Rhodanine; D000449:Aldehyde Reductase