Beneficial effects of the urinary trypsin inhibitor urinastatin on renal insults induced by gentamicin and mercuric chloride (HgCl2) poisoning.
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.
Ishigami
M
M
Department of Internal Medicine, Kanto Rosai Hospital, Kawasaki, Japan.
Eguchi
M
M
Yabuki
S
S
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*
D005839:Gentamicins; D006023:Glycoproteins; D014361:Trypsin Inhibitors; D008627:Mercuric Chloride; D012964:Sodium; C028665:urinastatin