PMID- 33658826
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220421
IS  - 1178-7031 (Print)
IS  - 1178-7031 (Electronic)
IS  - 1178-7031 (Linking)
VI  - 14
DP  - 2021
TI  - AST-120 Improves Cardiac Dysfunction in Acute Kidney Injury Mice via Suppression 
      of Apoptosis and Proinflammatory NF-kappaB/ICAM-1 Signaling.
PG  - 505-518
LID - 10.2147/JIR.S283378 [doi]
AB  - 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-1beta 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-1beta 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-kappaB/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-kappaB/ICAM-1 signaling.
CI  - (c) 2021 Shen et al.
FAU - Shen, Wen-Ching
AU  - Shen WC
AUID- ORCID: 0000-0003-0705-7467
AD  - Department of Basic Medicine, Putian University, Putian City, Fujian Province, 
      People's Republic of China.
FAU - Chou, Yu-Hsiang
AU  - Chou YH
AD  - Department of Internal Medicine, National Taiwan University Hospital Jin-Shan 
      Branch, New Taipei City, Taiwan.
FAU - Shi, Li-Shian
AU  - Shi LS
AD  - Department of Biotechnology, National Formosa University, Yun-Lin, Taiwan.
FAU - Chen, Zhi-Wei
AU  - Chen ZW
AD  - The Affiliated Hospital of Putian University, Putian City, Fujian Province, 
      People's Republic of China.
FAU - Tu, Hai-Jian
AU  - Tu HJ
AD  - The Affiliated Hospital of Putian University, Putian City, Fujian Province, 
      People's Republic of China.
FAU - Lin, Xin-Yi
AU  - Lin XY
AD  - Department of Basic Medicine, Putian University, Putian City, Fujian Province, 
      People's Republic of China.
FAU - Wang, Guei-Jane
AU  - Wang GJ
AD  - School of Medicine, Graduate Institute of Clinical Medical Science, China Medical 
      University, Taichung, 40402, Taiwan.
AD  - School of Medicine, Graduate Institute of Biomedical Sciences, China Medical 
      University, Taichung, 40402, Taiwan.
AD  - Department of Medical Research, China Medical University Hospital, Taichung, 
      40447, Taiwan.
AD  - Department of Health and Nutrition Biotechnology, Asia University, Taichung, 
      41354, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20210224
PL  - New Zealand
TA  - J Inflamm Res
JT  - Journal of inflammation research
JID - 101512684
PMC - PMC7917393
OTO - NOTNLM
OT  - AST-120
OT  - NF-kappaB
OT  - acute kidney injury
OT  - apoptosis
OT  - cardiac dysfunction
OT  - inflammation
COIS- The authors declare that they have no competing interests.
EDAT- 2021/03/05 06:00
MHDA- 2021/03/05 06:01
PMCR- 2021/02/24
CRDT- 2021/03/04 05:53
PHST- 2020/10/08 00:00 [received]
PHST- 2021/01/09 00:00 [accepted]
PHST- 2021/03/04 05:53 [entrez]
PHST- 2021/03/05 06:00 [pubmed]
PHST- 2021/03/05 06:01 [medline]
PHST- 2021/02/24 00:00 [pmc-release]
AID - 283378 [pii]
AID - 10.2147/JIR.S283378 [doi]
PST - epublish
SO  - J Inflamm Res. 2021 Feb 24;14:505-518. doi: 10.2147/JIR.S283378. eCollection 
      2021.