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AST-120 Improves Cardiac Dysfunction in Acute Kidney Injury Mice via Suppression of Apoptosis and Proinflammatory NF-κB/ICAM-1 Signaling

Authors Shen WC, Chou YH, Shi LS, Chen ZW, Tu HJ, Lin XY, Wang GJ

Received 8 October 2020

Accepted for publication 9 January 2021

Published 24 February 2021 Volume 2021:14 Pages 505—518

DOI https://doi.org/10.2147/JIR.S283378

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Ning Quan


Wen-Ching Shen,1 Yu-Hsiang Chou,2 Li-Shian Shi,3 Zhi-wei Chen,4 Hai-Jian Tu,4 Xin-yi Lin,1 Guei-Jane Wang5– 8

1Department of Basic Medicine, Putian University, Putian City, Fujian Province, People’s Republic of China; 2Department of Internal Medicine, National Taiwan University Hospital Jin-Shan Branch, New Taipei City, Taiwan; 3Department of Biotechnology, National Formosa University, Yun-Lin, Taiwan; 4The Affiliated Hospital of Putian University, Putian City, Fujian Province, People’s Republic of China; 5School of Medicine, Graduate Institute of Clinical Medical Science, China Medical University, Taichung, 40402, Taiwan; 6School of Medicine, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 40402, Taiwan; 7Department of Medical Research, China Medical University Hospital, Taichung, 40447, Taiwan; 8Department of Health and Nutrition Biotechnology, Asia University, Taichung, 41354, Taiwan

Correspondence: Guei-Jane Wang
School of Medicine, Graduate Institute of Clinical Medical Science, China Medical University, Taichung, 40402, Taiwan
Tel +886-422052121 ext. 4727
Fax +886-422251483
Email jennyw355@gmail.com
Wen-Ching Shen
Department of Basic Medicine, Putian University, 1133 Xueyuan Road, Chengxiang District, Putian City, Fujian Province, 351100, People’s Republic of China
Tel +86-13959593413
Fax +86-2768812
Email wenching8@gmail.com

Purpose: Acute kidney injury (AKI) is a devastating disorder associated with considerably high morbidity and mortality. Reports have shown that AST-120, an oral charcoal adsorbent, can reduce oxidative stress by lowering serum indoxyl sulfate levels. The effects of AST-120 and indoxyl sulfate on kidney injury and cardiac dysfunction were investigated in vivo and in vitro.
Patients and Methods: Patients were tracked for enrollment upon receiving a diagnosis of AKI. Plasma was collected to determine the renal and inflammatory parameters. Renal ischemia/reperfusion (I/R) induced AKI or sham operation was performed in C57BL/6J mice. Animals were divided into sham, AKI+vehicle, and AKI+AST-120 groups. Plasma and tissues were assembled after 48 h to assess apoptotic and inflammatory responses. We also conducted human umbilical vein endothelial cell (HUVECs) and HL-1 cardiomyocyte culture studies to determine the underlying mechanisms of indoxyl sulfate’s effects. Echocardiography, histopathology, biochemical indexes, ELISA, terminal dUTP nick-end labeling (TUNEL) and Western blot analysis were performed.
Results: The cohort included 25 consecutive patients with AKI and 25 non-AKI. Plasma levels of creatinine, indoxyl sulfate, IL-1β and ICAM-1 were significantly higher in patients with AKI than in non-AKI controls. Plasma levels of blood urea nitrogen, creatinine, indoxyl sulfate, IL-1β and renal tubular injury were increased in mice after renal I/R and were decreased by AST-120 treatment. In addition, AST-120 therapy not only improved the parameters assessed by echocardiography but also substantially attenuated the elevation of plasma BNP. Oral administration of AST-120 significantly downregulated NF-κB/ICAM-1 expression and reduced cell apoptosis in both kidney and heart after renal I/R injury.
Conclusion: Our investigations demonstrated that AST-120 administration improves cardiac dysfunction in AKI mice via the suppression of apoptosis and proinflammatory NF-κB/ICAM-1 signaling.

Keywords: acute kidney injury, cardiac dysfunction, AST-120, inflammation, apoptosis, NF-κB

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