ID 57526
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 Kakenhi
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.
Keywords
Acute renal failure
CYP3A2
dexamethasone
hepatic drug metabolism
midazolam
Note
This fulltext will be available in Aug 2020
Published Date
2019-08-28
Publication Title
Xenobiotica
Publisher
TAYLOR & FRANCIS
Start Page
1
End Page
9
ISSN
0049-8254
NCID
AA00891766
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
File Version
author
PubMed ID
DOI
Web of Sience KeyUT
Related Url
isVersionOf https://doi.org/10.1080/00498254.2019.1655680
Funder Name
Japan Society for the Promotion of Science
助成番号
24590192
15K08097
19K07220