Evaluation of the Effect of Uremic Serum on Hepatic Reductase Functional Expression

Author(s): Osama Y. Alshogran*, Esra`a F. Al-Obaidi, Belal A. Al-Husein, Ashraf O. Oweis.

Journal Name: Drug Metabolism Letters

Volume 12 , Issue 1 , 2018

Become EABM
Become Reviewer

Graphical Abstract:


Background: The nonrenal clearance of drugs mediated by hepatic reduction is selectively altered by kidney disease. This study evaluated the influence of uremic serum on the expression and activity of reductase enzymes.

Methods: Human hepatocellular carcinoma cells (HepG2) were incubated with 5% pooled serum collected from patients with hemodialysis (pre- and post-dialysis session) or control subjects. The mRNA expression of various aldo-keto (AKR1C) and carbonyl (CBR) reductases were measured. Reductase metabolic activity was assessed in human liver cytosol or HepG2 cells using naltrexone as a substrate.

Results: Incubation of cells with pre-dialysis serum resulted in significant upregulation of AKR1C4 (by 63.2%) and CBR1 (by 34.6%) versus control serum. This increase was not observed for AKR1C1 and CBR1 with serum collected post-dialysis. While uremic serum had no effect on reductase activity, some instances with differences in metabolite formation among individual’s pre- and post-dialysis samples were observed.

Conclusion: Although uremic serum can upregulate mRNA expression of several reductases, this effect was not observed at the activity level. Future studies are necessary to improve our understanding of the mechanistic effects of impaired kidney function on drug reduction.

Keywords: Hemodialysis, uremic serum, drug metabolism, reduction, activity, expression.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2018
Page: [75 - 81]
Pages: 7
DOI: 10.2174/1872312812666180416154436
Price: $58

Article Metrics

PDF: 30