Effects of Cyclosporin on Kidney Glutathione Metabolism and Cytochrome P-450 in the Rabbit: Possible Implication of Eicosanoid Metabolism
| Autor: | H. Dutertre-Catella, Jean-Michel Warnet, F. Massicot, J. R. Claude, M. Thevenin, C. Martin |
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| Rok vydání: | 1994 |
| Předmět: |
medicine.medical_specialty
Health Toxicology and Mutagenesis Renal cortex Glutathione reductase Biology Toxicology Nephrotoxicity chemistry.chemical_compound Cytochrome P-450 Enzyme System Internal medicine Cyclosporin a medicine Animals Pharmacology chemistry.chemical_classification Kidney Chemical Health and Safety Eicosanoid metabolism Glutathione peroxidase Public Health Environmental and Occupational Health General Medicine Glutathione Endocrinology medicine.anatomical_structure chemistry Cyclosporine Eicosanoids Female Kidney Diseases Rabbits |
| Zdroj: | Drug and Chemical Toxicology. 17:449-462 |
| ISSN: | 1525-6014 0148-0545 |
| DOI: | 10.3109/01480549409014311 |
| Popis: | This study was designed to assess Cyclosporin A (CsA) nephrotoxicity in the rabbit-possibly a more sensitive species than the rat-and to explore the mechanism of this toxicity with special attention to glutathione metabolism disturbances and cytochrome P-450 level in the kidney. CsA given for three days at a daily dose of 50 mg/kg (s.c.) induced nephrotoxicity as assessed by histological abnormalities and by a significant increase in blood urea nitrogen and urinary enzyme activities: N-acetyl-beta-D-glucosaminidase and L-gamma-glutamyl-transferase. This observed renal injury was of the same order as that obtained in the rat. In addition, there was a significant increase in oxidized glutathione content (40%) while reduced glutathione level remained unchanged. Concurrently, there was a significant decrease in renal cortex glutathione reductase (49%) and to a lesser extent in glutathione peroxidase activities (16%) whereas that of glutathione-S-transferase was not modified. A significant increase in renal cortex cytochrome P-450 (3-fold versus controls) was also observed. The mechanism of CsA nephrotoxicity is to be related to a cytochrome P-450 induction. This event could induce the observed impairments in renal glutathione metabolism and Na+K(+)-ATPase activity, via a possible increase in eicosanoid metabolism. |
| Databáze: | OpenAIRE |
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