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.
Keywords: Activity, end-stage renal disease, enzyme kinetics, expression, hepatic reductases, nonrenal clearance.
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