Functional and Histopathologic Effects of Rapamycin on Mouse Kidney
| Autor: | J. F. Did Joseph, S. N. Sehgal |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Male
Pathology medicine.medical_specialty Ratón Immunology Renal function Polyenes Kidney Toxicology Blood Urea Nitrogen Elevated bun Mice Internal medicine medicine Animals Immunology and Allergy Sirolimus Pharmacology Mice Inbred BALB C Mice Inbred C3H business.industry General Medicine Endocrinology medicine.anatomical_structure Vacuolization Toxicity Cyclosporine Mouse Kidney Female Histopathology business Immunosuppressive Agents |
| Zdroj: | Immunopharmacology and Immunotoxicology. 15:45-56 |
| ISSN: | 1532-2513 0892-3973 |
| DOI: | 10.3109/08923979309066932 |
| Popis: | The effect of rapamycin (RAPA) on kidney function and histopathology was assessed in two strains of mice. Male C3H/HeJ mice were treated with RAPA for 4 days at doses of 25, 50, 75, and 100 mg/kg, ip and male C3H/HeJ or female Balb/cJ mice were both treated for 7 days at doses of 75, 150 and 200 mg/kg. Cyclosporine (CsA) was also administered to female Balb/cJ mice at doses of 50, 100, 150 and 200 mg/kg, ip. RAPA-treated mice had elevated BUN levels but the effect was not dose-dependent and was not present in the high dose, 7-day study conducted in the C3H/HeJ mice. Body weights were significantly depressed in both of the 7 day studies but not in the 4 day study. Histopathologic examination of the kidneys revealed the presence of intracytoplasmic vacuolization in the proximal tubules in both of the 7 day studies at the higher dose only. There were no drug-related deaths. In the CsA-treated mice, multiple deaths were recorded in both the 150 mg/kg and 200 mg/kg dose groups, probably related to neurotoxicity, and BUN levels were elevated in the 100 mg/kg dose group. In conclusion, RAPA's effects on kidney function were minimal at doses 50 times higher than its therapeutic dose established in the mouse. RAPA exhibited a better therapeutic index than CsA in the mouse. |
| Databáze: | OpenAIRE |
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