Journal
JOURNAL OF INFLAMMATION RESEARCH
Volume 14, Issue -, Pages 505-518Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/JIR.S283378
Keywords
acute kidney injury; cardiac dysfunction; AST-120; inflammation; apoptosis; NF-kappa B
Categories
Funding
- Ministry of Science and Technology [MOST 104-2314-B-002-119-MY3, MOST 108-2635-B-039-002]
- China Medical University [CMU108-MF-18]
- China Medical University Hospital [DMR-107-113]
- Putian University [2019118]
- Mrs. Hsiu-Chin Lee Kidney Research Foundation
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The study demonstrates that AST-120 treatment can alleviate kidney and heart damage in AKI patients by reducing harmful substance levels in plasma, improving inflammatory responses, and significantly reducing cardiac burden.
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-1 beta 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-1 beta 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-kappa B/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-kappa B/ICAM-1 signaling.
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