Proteasome participates in the pathogenesis of ischemic acute renal failure in rats
| Autor: | Seiya Hayashi, Yasuo Matsumura, Masanori Takaoka, Makoto Itoh, Toshihiko Kuro |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty Proteasome Endopeptidase Complex Urinary system medicine.medical_treatment Ischemia Renal function urologic and male genital diseases Kidney Rats Sprague-Dawley Multienzyme Complexes Internal medicine medicine Animals Enzyme Inhibitors Blood urea nitrogen Pharmacology Dose-Response Relationship Drug business.industry Calpain Dipeptides Acute Kidney Injury medicine.disease Nephrectomy Rats Cysteine Endopeptidases medicine.anatomical_structure Endocrinology Proteasome inhibitor business Oligopeptides medicine.drug Kidney disease |
| Zdroj: | European journal of pharmacology. 384(1) |
| ISSN: | 0014-2999 |
| Popis: | Acute renal failure was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function parameters such as blood urea nitrogen, plasma creatinine, creatinine clearance, urine flow and urinary osmolality were measured to test the effectiveness of drugs. Renal function in untreated acute renal failure rats markedly decreased at 24 h after reperfusion. The administration of PSI, N-benzyloxycarbonyl-Ile-Glu(O-t-Bu)-Ala-leucinal, a proteasome inhibitor, at a dose of 1 mg/kg before the occlusion abolished the decreases in the renal function of acute renal failure rats. Calpeptin (1 mg/kg), a calpain inhibitor, attenuated the deterioration of renal function to the same extent as 0.1 mg/kg PSI, but no significant difference was observed between the untreated and calpeptin-treated acute renal failure groups. Histopathological examination of the kidney of untreated acute renal failure rats revealed severe lesions, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion, all of which were significantly suppressed by PSI (1 mg/kg) treatment. In contrast, calpeptin, at the same dose, was ineffective against the development of renal lesions. These results suggest that proteasome participates in the pathogenesis of ischemic acute renal failure. Thus, proteasome may be a potential target for the identification of agents that may be useful in the treatment of diseases whose etiology is dependent on ischemia/reperfusion. |
| Databáze: | OpenAIRE |
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