Acetylbritannilactone attenuates contrast-induced acute kidney injury through its anti-pyroptosis effects.

Abstract

Contrast-induced acute kidney injury (CI-AKI) is a severe complication caused by intravascular applied radial contrast media (CM). Pyroptosis is a lytic type of cell death inherently associated with inflammation response and the secretion of pro-inflammatory cytokines following caspase-1 activation. The aim of the present study was to investigate the protective effects of acetylbritannilactone (ABL) on iopromide (IOP)-induced acute renal failure and reveal the underlying mechanism. In vivo and in vitro, IOP treatment caused renal damage and elevated the caspase-1 (+) propidium iodide (PI) (+) cell count, interleukin (IL)-1β and IL-18 levels, lactate dehydrogenase (LDH) release, and the relative expression of nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and gasdermin D (GSDMD), suggesting that IOP induces AKI via the activation of pyroptosis. Furthermore, the pretreatment of ABL partly mitigated the CI-AKI, development of pyroptosis, and subsequent kidney inflammation. These data revealed that ABL partially prevents renal dysfunction and reduces pyroptosis in CI-AKI, which may provide a therapeutic target for the treatment of CM-induced AKI.

• Authors: Fei Chen, Jingchao Lu, Xiuchun Yang, Bing Xiao, Huiqiang Chen, Weina Pei, Yaqiong Jin, Mengxiao Wang, Yue Li, Jie Zhang, Fan Liu, Guoqiang Gu, Wei Cui
• Journal: Bioscience reports (Biosci Rep) Vol. 40 Issue 2 (02 28 2020) ISSN: 1573-4935 [Electronic] England
• PMID: 31998952 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Author(s).

Chemical References

• Apoptosis Regulatory Proteins
• Inflammation Mediators
• Lactones
• acetylbritannilatone
• Iohexol
• iopromide

Topics

• Acute Kidney Injury (chemically induced, metabolism, pathology, prevention & control)
• Animals
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Cell Line
• Disease Models, Animal
• Epithelial Cells (drug effects, metabolism, pathology)
• Humans
• Inflammation Mediators (metabolism)
• Iohexol (analogs & derivatives)
• Kidney Tubules (drug effects, metabolism, pathology)
• Lactones (pharmacology)
• Male
• Mice, Inbred C57BL
• Pyroptosis (drug effects)
• Signal Transduction