Back to Search
Start Over
Downregulation of Hepatic Carbonyl Reductase Type 1 in End-Stage Renal Disease.
- Source :
-
Drug metabolism letters [Drug Metab Lett] 2015; Vol. 9 (2), pp. 111-8. - Publication Year :
- 2015
-
Abstract
- The functional expression of several hepatic drug metabolizing enzymes and transporters are altered in patients with end-stage renal disease (ESRD). We aimed to assess the effect of ESRD on the expression and function of hepatic reductases. Cytosolic and microsomal fractions were isolated from liver tissue from deceased ESRD (n=10) and deceased control patients (n=11). Gene and protein expression, and metabolic activity of reductases were assessed by conducting qRT-PCR, Western blotting and enzyme kinetics, respectively. A 65% decrease in carbonyl reductase 1 protein expression (p<0.05), and a trend toward decreased reductase mRNA expression and activity was observed in ESRD livers versus controls. These results demonstrate a trend toward decreased functional expression of selective hepatic reductases in ESRD livers, which may partially explain altered pharmacokinetics of CBR1 drug substrates in ESRD. Future studies with larger sample size are warranted to confirm these findings.
- Subjects :
- Aged
Alcohol Oxidoreductases genetics
Case-Control Studies
Down-Regulation
Female
Gene Expression Regulation, Enzymologic
Humans
Kidney Failure, Chronic complications
Kidney Failure, Chronic diagnosis
Kidney Failure, Chronic genetics
Kidney Failure, Chronic mortality
Kinetics
Male
Middle Aged
Oxidation-Reduction
RNA, Messenger metabolism
Substrate Specificity
Warfarin metabolism
Alcohol Oxidoreductases metabolism
Kidney Failure, Chronic enzymology
Liver enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1874-0758
- Volume :
- 9
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Drug metabolism letters
- Publication Type :
- Academic Journal
- Accession number :
- 26282591
- Full Text :
- https://doi.org/10.2174/1872312809666150818111626