RGD Reference Report - Protective effect of human ulinastatin against gentamicin-induced acute renal failure in rats. - Rat Genome Database

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Protective effect of human ulinastatin against gentamicin-induced acute renal failure in rats.

Authors: Nakakuki, M  Yamasaki, F  Shinkawa, T  Kudo, M  Watanabe, M  Mizota, M 
Citation: Nakakuki M, etal., Can J Physiol Pharmacol. 1996 Jan;74(1):104-11.
RGD ID: 6904218
Pubmed: PMID:8963945   (View Abstract at PubMed)

We investigated the protective effect of human ulinastatin against gentamicin-induced acute renal failure in rats. Gentamicin sulfate was subcutaneously injected at a dose of 200 mg/kg for 5 consecutive days. After 3 days administration of gentamicin, a slight decrease in renal function was observed, as well as granulovascular degeneration in the proximal tubular cells as a change in the renal histology. After 5 days administration of gentamicin, a remarkable increase in plasma concentration of creatinine (from 0.27 +/- 0.02 to 1.17 +/- 0.18 mg/dL) and urea nitrogen (from 17.8 +/- 0.6 to 48.8 +/- 5.1 mg/dL) and a significant decrease in creatinine clearance (from 0.64 +/- 0.08 to 0.20 +/- 0.03 mL.100 g-1.min-1) were observed. In addition, an apparent increase in urinary excretion of N-acetyl-beta-D-glucosaminidase and albumin was detected. In the renal histology, proximal tubular necrosis and desquamation of the epithelial cells in the cortex were observed. Furthermore, hyaline cast formation was frequently observed in the outer stripe of the outer medulla. Ulinastatin at doses of 100,000 or 300,000 U/kg was coadministered intraperitoneally just after each gentamicin injection. Ulinastatin treatment showed a dose-dependent suppression of gentamicin-induced biochemical alterations and histological changes. After 5 days treatment with 300,000 U.kg-1.day-1 of ulinastatin, the magnitude of gentamicin-induced changes in renal function was significantly lessened, by 45-80%. The score for proximal tubular injuries and the rate of hyaline cast formation were also significantly lower in the same group of animals than those in the group treated with gentamicin alone. In the in vitro study, ulinastatin at 10-300 U/mL showed a concentration-dependent suppression on the fragility of the lysosomal membrane isolated from rat kidney cortex during hypotonic treatment. These results indicate that human ulinastatin has a prominent protective effect on gentamicin-induced acute renal failure in rats, and the lysosomal membrane stabilizing effect is possibly involved as a mechanism of this action.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AMBPHumanacute kidney failure  IMP  RGD 
AmbpRatacute kidney failure  ISOAMBP (Homo sapiens) RGD 
AmbpMouseacute kidney failure  ISOAMBP (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ambp  (alpha-1-microglobulin/bikunin precursor)

Genes (Mus musculus)
Ambp  (alpha 1 microglobulin/bikunin precursor)

Genes (Homo sapiens)
AMBP  (alpha-1-microglobulin/bikunin precursor)


Additional Information