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Vitamin C alleviates LPS-induced myocardial injury by inhibiting pyroptosis via the ROS-AKT/mTOR signalling pathway

BACKGROUND: The efficacy of vitamin C in sepsis remains controversial. Whether vitamin C can alleviate lipopolysaccharide (LPS)-induced myocardial injury by inhibiting pyroptosis has not been studied. This study aimed to evaluate the effects of vitamin C on LPS-induced myocardial injury in vitro. ME...

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Detalles Bibliográficos
Autores principales: Zhang, Pu, Zang, Meirong, Sang, Zhenzhen, Wei, Yunxia, Yan, Yan, Bian, Xiaohua, Dong, Shimin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783737/
https://www.ncbi.nlm.nih.gov/pubmed/36550401
http://dx.doi.org/10.1186/s12872-022-03014-9
Descripción
Sumario:BACKGROUND: The efficacy of vitamin C in sepsis remains controversial. Whether vitamin C can alleviate lipopolysaccharide (LPS)-induced myocardial injury by inhibiting pyroptosis has not been studied. This study aimed to evaluate the effects of vitamin C on LPS-induced myocardial injury in vitro. METHODS: H9C2 cells were treated with indicated concentrations of LPS, and the cell viability was then assessed by CCK-8 assay. The levels of lactate dehydrogenase (LDH), CK-MB, IL-18 and IL-1β were examined by enzyme-linked immunosorbent assay (ELISA). The levels of intracellular reactive oxygen species (ROS) were measured using the fluorescent probe dichlorodihydrofluorescein diacetate (DCFH-DA). Western blot assays were conducted to determine the levels of the ROS-associated protein nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) and pyroptosis-associated proteins, such as NOD-like receptor (NLR) family pyrin domain containing 3 (NLRP3), caspase-1 and gasdermin D (GSDMD). The AKT inhibitor MK-2206 was then applied to explore the signalling pathway. Finally, H9C2 cells were divided into the control group, LPS group, vitamin C + LPS group, and N-acetyl-l-cysteine (NAC) + LPS group. The intracellular ROS, levels of associated proteins, cell viability, and release of LDH, CK-MB, IL-18 and IL-1β were examined. RESULTS: LPS decreased cell viability and induced ROS and pyroptosis in H9C2 cells in a dose-dependent manner. Moreover, LPS activated the AKT/mTOR pathway in H9C2 cells. The AKT inhibitor MK-2206 protected H9C2 cells from LPS-induced death by suppressing pyroptosis, without changing intracellular ROS level. Vitamin C significantly inhibited intracellular ROS and cell pyroptosis in LPS-treated H9C2 cells. Moreover, vitamin C suppressed the activation of the AKT/mTOR pathway. CONCLUSIONS: Our data suggest that vitamin C alleviates LPS-induced myocardial injury by inhibiting pyroptosis via the ROS-AKT/mTOR signalling pathway and thus provide novel insights into the prevention of sepsis-induced myocardial dysfunction. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-022-03014-9.