The effect of chronic kidney disease on CYP2B expression and activity in male Wistar rats.
Adenine
/ adverse effects
Animals
Aryl Hydrocarbon Hydroxylases
/ genetics
Bupropion
/ pharmacokinetics
Cytochrome P-450 CYP2B1
/ genetics
Disease Models, Animal
Down-Regulation
Gene Expression Regulation, Enzymologic
Male
Microsomes, Liver
/ metabolism
Rats
Rats, Wistar
Renal Insufficiency, Chronic
/ chemically induced
Steroid Hydroxylases
/ genetics
chronic kidney disease
cytochrome P450
hepatic drug metabolism
nonrenal clearance
Journal
Pharmacology research & perspectives
ISSN: 2052-1707
Titre abrégé: Pharmacol Res Perspect
Pays: United States
ID NLM: 101626369
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
25
03
2019
accepted:
02
04
2019
entrez:
4
5
2019
pubmed:
3
5
2019
medline:
8
2
2020
Statut:
epublish
Résumé
Chronic kidney disease (CKD) is characterized by progressive reduction in kidney function over time. CKD affects greater than 10% of the population and its incidence is on the rise due to the growing prevalence of its risk factors. Previous studies demonstrated CKD alters nonrenal clearance of drugs in addition to reducing renal clearance. We assessed the function and expression of hepatic CYP2B enzymes using a rat model of CKD. CKD was induced in Wistar rats by supplementing their chow with adenine and confirmed through the detection of elevated uremic toxins in plasma. Liver enzymes AST and ALT were unchanged by the adenine diet. Bupropion was used as a probe substrate for hepatic CYP2B function using rat liver microsomes. The resulting metabolite, hydroxy-bupropion, and bupropion were quantified by ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry. Level of mRNA and protein were determined by RT-PCR and Western blot, respectively. The results of our study demonstrate that CYP2B1 is downregulated in a rat model of CKD. CYP2B1 mRNA level was significantly decreased (88%,
Identifiants
pubmed: 31049204
doi: 10.1002/prp2.475
pii: PRP2475
pmc: PMC6484215
doi:
Substances chimiques
Bupropion
01ZG3TPX31
Steroid Hydroxylases
EC 1.14.-
Aryl Hydrocarbon Hydroxylases
EC 1.14.14.1
Cytochrome P-450 CYP2B1
EC 1.14.14.1
steroid 16-beta-hydroxylase
EC 1.14.14.1
Adenine
JAC85A2161
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e00475Déclaration de conflit d'intérêts
None declared.
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