ID | 57526 |
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Author |
Doi, Masami
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kajikawa, Noriko
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Aiba, Tetsuya
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Abstract | The inductive effects of dexamethasone on hepatic midazolam metabolism were examined in Wistar rats with acute renal failure (ARF) to clarify whether the ARF-related decrease in the hepatic expression of drug-metabolizing enzymes is caused by an impairment in the translation/polypeptide formation process. ARF was induced with intramuscular glycerol injection. Dexamethasone was orally administered. Pooled liver microsomes from five rats were prepared with ultracentrifugation for each of four groups, namely, control and ARF rats, control rats with dexamethasone treatment and ARF rats with dexamethasone treatment. Hepatic drug-metabolizing activity was examined in an incubation study with the microsomes, where midazolam was employed as a substrate of cytochrome P450 (CYP) 3A enzymes. The hepatic protein and mRNA expressions of CYP3A23/3A1 and 3A2 enzymes were also evaluated. With dexamethasone treatment, the hepatic metabolic rate of midazolam increased 1.4 times in control rats, while it increased 19.6 times in ARF rats, reflecting the greater induction of hepatic protein expressions of CYP3A enzymes in ARF rats than in control rats. The hepatic protein expression process for CYP3A23/3A1 and 3A2 responds well to dexamethasone treatment in ARF rats, indicating that the translation/polypeptide formation process is not impaired in the presence of ARF.
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Keywords | Acute renal failure
CYP3A2
dexamethasone
hepatic drug metabolism
midazolam
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Note | This article has been accepted for publication in Xenobiotica, published by Taylor & Francis.
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Published Date | 2019-08-28
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Publication Title |
Xenobiotica
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Publisher | Taylor & Francis
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Start Page | 1
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End Page | 9
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ISSN | 0049-8254
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NCID | AA00891766
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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File Version | author
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DOI | |
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Related Url | isVersionOf https://doi.org/10.1080/00498254.2019.1655680
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Funder Name |
Japan Society for the Promotion of Science
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助成番号 | 24590192
15K08097
19K07220
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