title: Beneficial effects of the urinary trypsin inhibitor urinastatin on renal insults induced by gentamicin and mercuric chloride (HgCl2) poisoning.
abstract: The authors investigated the protective effects of the urinary trypsin inhibitor urinastatin on acute renal failure induced in rats by gentamicin (240 mg/kg body weight i.p. for 3 days) and by mercuric chloride (3 mg/kg s.c.). In rats injected with gentamicin, glomerular filtration rate (GFR), renal plasma flow (RPF), and percent fractional sodium excretion (%FENa) were 151 +/- 51 microliters/min/100 g body weight, 0.69 +/- 0.31 ml/min/100 g and 0.73 +/- 0.32, respectively, whereas in rats given 100,000 U of urinastatin the renal function was significantly ameliorated (GFR 318 +/- 43 microliters/min/100 g RPF 1.41 +/- 0.35 ml/min/100 g), although the %FENa (0.46 +/- 0.26) was not significantly improved. A 50,000-unit dose of urinastatin prevented the deterioration of renal function to some extent following administration of gentamicin: GFR 219 +/- 66 microliters/min/100 g and RPF 0.93 +/- 0.43 ml/min/100 g. In the study using mercuric chloride, treatment with 75,000 U of urinastatin protected the kidney from HgCl2 poisoning, yielding values of 294 +/- 93 microliters/min/100 g (GFR), 1.03 +/- 0.41 ml/min/100 g (RPF), and 1.44 +/- 0.72 microliters/min/100 g (%FENa) as compared with respective values of 169 +/- 48 microliters/min/100 g, 0.7 +/- 0.18 ml/min/100 g, and 2.22 +/- 1.35 in the untreated rats. Renal histology revealed mild to moderate tubular epithelial changes in untreated rats, but preservation of an almost normal tubular structure in urinastatin-treated rats in both studies.
authors.affiliation: Department of Internal Medicine, Kanto Rosai Hospital, Kawasaki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ishigami
authors.forename: M
authors.initials: M
authors.lastname: Eguchi
authors.forename: S
authors.initials: S
authors.lastname: Yabuki
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005839:Gentamicins / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006023:Glycoproteins / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012964:Sodium / Q000652:urine; D014361:Trypsin Inhibitors / Q000494:pharmacology*
chemical_list: D005839:Gentamicins; D006023:Glycoproteins; D014361:Trypsin Inhibitors; D008627:Mercuric Chloride; D012964:Sodium; C028665:urinastatin