Changes of hepatic microsomal oxidative drug metabolizing enzymes in chronic renal failure (CRF) rats by partial nephrectomy
| Autor: | Hajime Yasuhara, Ken Shimada, Eiji Uchida, Kuninobu Yasuda, Yuki Nishimura, Naoki Uchida, Norimitsu Kurata, Masahisa Hashimoto |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Corticotropin-Releasing Hormone Metabolite medicine.medical_treatment Microdialysis Blotting Western Renal function Trimethadione Nephrectomy Rats Sprague-Dawley chemistry.chemical_compound Cytochrome P-450 Enzyme System Internal medicine medicine Animals Blood urea nitrogen Pharmacology Creatinine biology Dose-Response Relationship Drug Cytochrome P450 Rats Enzyme Activation Endocrinology chemistry Liver Pharmaceutical Preparations biology.protein Drug metabolism medicine.drug |
| Zdroj: | Japanese journal of pharmacology. 68(4) |
| ISSN: | 0021-5198 |
| Popis: | Male SD rats, 7-weeks-old, were used to investigate the changes in the hepatic drug metabolizing system of chronic renal failure (CRF) model rats. Partial nephrectomy (5/6) was performed in a two-stage surgical procedure. After nephrectomy, the rats were housed under regular conditions at least 21 days. After confirming the CRF states, trimethadione (TMO, 100 mg/kg, i.p.) was administered for evaluation of the hepatic drug metabolizing capacity; the ratio of dimethadione (DMO: the only metabolite of TMO) to TMO (DMO/TMO) in the serum and the dialysate from the blood microdialysis method were ascertained. The hepatic drug metabolizing enzyme contents and activities were also determined. In the CRF rats, the DMO/TMO ratios decreased significantly; total cytochrome P450 (CYP) contents, aminopyrine N-demethylase activity and δ-aminolevulinic acid synthetase activity also decreased significantly in the CRF rats. The extent of the alterations of these enzyme contents and activities correlated well with the severity of the CRF states evaluated by the serum blood urea nitrogen and creatinine concentrations. With Western blot analysis, the levels of CYP2C6, CYP2C11 and CYP3A2 decreased considerably in the CRF rats. These results suggest that CRF states induce not only a reduction of renal function but also an alteration of hepatic metabolism. |
| Databáze: | OpenAIRE |
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