Iodinated contrast is used for imaging and invasive procedures and it can cause contrast
induced acute kidney injury (CI-AKI), which is the third leading hospital-acquired
health problem. The purpose of the present study was to determine the effect of α-adrenergic
receptor-1b (Adra1b) inhibition by using terazosin on change in kidney function, gene, and protein expression
in C57BL/6J male mice, 6-8 weeks with chronic kidney disease (CKD). CKD was induced
by surgical nephrectomy. Twenty eight days later, 100-µL of iodinated contrast (CI
group) or saline (S group) was given via the carotid artery. Whole-transcriptome RNA-sequencing
(RNA-Seq) analysis of the kidneys was performed at day 2. Mice received either 50-µL
of saline ip or terazosin (2 mg/kg) in 50-µL of saline ip 1 hour before contrast administration
which was continued every 12 hours until the animals were euthanized 2 and 7 days
later. The kidneys were removed for gene expression, immunohistochemical analysis,
and blood serum analyzed for kidney function. Differential gene expression analysis
identified 21 upregulated and 436 downregulated genes (fold change >2; P < 0.05) that were common to all sample (n = 3 for both contrast and saline). We identified
Adra1b using bioinformatic analysis. Mice treated with terazosin had a significant decrease
in serum creatinine, urinary Kim-1 levels, HIF-1α, apoptosis, and downstream Adrab1 genes including Ece1, Edn1, pMAPK14 with increased cell proliferation. Contrast exposure upregulated Adra1b gene expression in HK-2 cells. Inhibition of Adra1b with terazosin abrogated Ece1, Edn1, and contrast-induced Fsp-1, Mmp-2, Mmp-9 expression, and caspase-3/7 activity in HK-2 cells.
Abbreviations:
Adra1b (α-adrenergic receptor-1b), CI-AKI (Contrast induced acute kidney injury), HK-2 cells (Human kidney proximal tubule cells), CKD (chronic kidney disease)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: March 08, 2021
Accepted:
March 6,
2021
Received in revised form:
January 24,
2021
Received:
October 16,
2020
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
