Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction

Cardiac dysfunction is a common complication of sepsis, and is attributed to severe inflammatory responses. Ferroptosis is reported to be involved in sepsis-induced cardiac inflammation. Therefore, we speculated that ferrostatin-1 (Fer-1), a ferroptosis inhibitor, improves cardiac dysfunction caused...

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Autores principales:	Zheng Xiao, Bin Kong, Jin Fang, Tianyou Qin, Chang Dai, Wei Shuai, He Huang
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	ferroptosis inflammation ferrostatin-1 cardiac dysfunction Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/231be07b67e94d19ade5f97d55f5a55e
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spelling	oai:doaj.org-article:231be07b67e94d19ade5f97d55f5a55e2021-12-01T14:41:00ZFerrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction2165-59792165-598710.1080/21655979.2021.2001913https://doaj.org/article/231be07b67e94d19ade5f97d55f5a55e2021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.2001913https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Cardiac dysfunction is a common complication of sepsis, and is attributed to severe inflammatory responses. Ferroptosis is reported to be involved in sepsis-induced cardiac inflammation. Therefore, we speculated that ferrostatin-1 (Fer-1), a ferroptosis inhibitor, improves cardiac dysfunction caused by sepsis. An intraperitoneal injection of lipopolysaccharide (LPS) was performed to induce a rat cardiac dysfunction model. Echocardiography, cardiac histopathology, biochemical and western blot results were analyzed. Twelve hours after the LPS injection, LPS-treated rats exhibited deteriorating cardiac systolic function, increased levels of cardiac injury markers and levels of ferroptosis markers prostaglandin endoperoxide synthase 2 (PTGS2). Additionally, LPS increased iron deposition in the myocardium, with downregulating ferroportin (FPN, SLC40A1) and transferrin receptor (TfR)expression, and upregulating ferritin light chain (FTL) and ferritin heavy chain (FTH1) expression. Meanwhile, LPS also increased lipid peroxidation in the rat heart by decreasing the expression of glutathione peroxidase 4 (GPX4). Moreover, the expression of inflammatory cytokines, such as tumor necrosis-alpha (TNF-α), interleukin-1 (IL-1β), and interleukin-6 (IL-6), and inflammatory cell infiltration were also increased following LPS challenge. Finally, the abovementioned adverse effects of LPS were relieved by Fer-1 except for TfR expression. Mechanistically, Fer-1 significantly reduced the levels of toll-like receptor 4 (TLR4), phospho-nuclear factor kappa B (NF-κB), and phospho-inhibitor of kappa Bα (IκBα) in LPS-treated rats. In summary, these findings imply that Fer-1 improved sepsis-induced cardiac dysfunction at least partially via the TLR4/NF-κB signaling pathway.Zheng XiaoBin KongJin FangTianyou QinChang DaiWei ShuaiHe HuangTaylor & Francis Grouparticleferroptosisinflammationferrostatin-1cardiac dysfunctionBiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 2, Pp 9367-9376 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ferroptosis inflammation ferrostatin-1 cardiac dysfunction Biotechnology TP248.13-248.65
spellingShingle	ferroptosis inflammation ferrostatin-1 cardiac dysfunction Biotechnology TP248.13-248.65 Zheng Xiao Bin Kong Jin Fang Tianyou Qin Chang Dai Wei Shuai He Huang Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction
description	Cardiac dysfunction is a common complication of sepsis, and is attributed to severe inflammatory responses. Ferroptosis is reported to be involved in sepsis-induced cardiac inflammation. Therefore, we speculated that ferrostatin-1 (Fer-1), a ferroptosis inhibitor, improves cardiac dysfunction caused by sepsis. An intraperitoneal injection of lipopolysaccharide (LPS) was performed to induce a rat cardiac dysfunction model. Echocardiography, cardiac histopathology, biochemical and western blot results were analyzed. Twelve hours after the LPS injection, LPS-treated rats exhibited deteriorating cardiac systolic function, increased levels of cardiac injury markers and levels of ferroptosis markers prostaglandin endoperoxide synthase 2 (PTGS2). Additionally, LPS increased iron deposition in the myocardium, with downregulating ferroportin (FPN, SLC40A1) and transferrin receptor (TfR)expression, and upregulating ferritin light chain (FTL) and ferritin heavy chain (FTH1) expression. Meanwhile, LPS also increased lipid peroxidation in the rat heart by decreasing the expression of glutathione peroxidase 4 (GPX4). Moreover, the expression of inflammatory cytokines, such as tumor necrosis-alpha (TNF-α), interleukin-1 (IL-1β), and interleukin-6 (IL-6), and inflammatory cell infiltration were also increased following LPS challenge. Finally, the abovementioned adverse effects of LPS were relieved by Fer-1 except for TfR expression. Mechanistically, Fer-1 significantly reduced the levels of toll-like receptor 4 (TLR4), phospho-nuclear factor kappa B (NF-κB), and phospho-inhibitor of kappa Bα (IκBα) in LPS-treated rats. In summary, these findings imply that Fer-1 improved sepsis-induced cardiac dysfunction at least partially via the TLR4/NF-κB signaling pathway.
format	article
author	Zheng Xiao Bin Kong Jin Fang Tianyou Qin Chang Dai Wei Shuai He Huang
author_facet	Zheng Xiao Bin Kong Jin Fang Tianyou Qin Chang Dai Wei Shuai He Huang
author_sort	Zheng Xiao
title	Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction
title_short	Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction
title_full	Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction
title_fullStr	Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction
title_full_unstemmed	Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction
title_sort	ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/231be07b67e94d19ade5f97d55f5a55e
work_keys_str_mv	AT zhengxiao ferrostatin1alleviateslipopolysaccharideinducedcardiacdysfunction AT binkong ferrostatin1alleviateslipopolysaccharideinducedcardiacdysfunction AT jinfang ferrostatin1alleviateslipopolysaccharideinducedcardiacdysfunction AT tianyouqin ferrostatin1alleviateslipopolysaccharideinducedcardiacdysfunction AT changdai ferrostatin1alleviateslipopolysaccharideinducedcardiacdysfunction AT weishuai ferrostatin1alleviateslipopolysaccharideinducedcardiacdysfunction AT hehuang ferrostatin1alleviateslipopolysaccharideinducedcardiacdysfunction
_version_	1718404981641445376

Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction

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