Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction
Autor: | Tianyou Qin, Chang Dai, Bin Kong, Jin Fang, Zheng Xiao, He Huang, Wei Shuai |
---|---|
Rok vydání: | 2021 |
Předmět: |
Lipopolysaccharides
Male medicine.medical_specialty Systole Bioengineering Transferrin receptor Inflammation Phenylenediamines Applied Microbiology and Biotechnology Proinflammatory cytokine Sepsis Electrocardiography ferrostatin-1 NF-KappaB Inhibitor alpha Internal medicine medicine Animals Ferroptosis Rats Wistar FTH1 Cyclohexylamines biology cardiac dysfunction business.industry Myocardium NF-kappa B Heart General Medicine medicine.disease Survival Analysis Ferritin Ferritin light chain Toll-Like Receptor 4 Endocrinology biology.protein TLR4 lipids (amino acids peptides and proteins) medicine.symptom business TP248.13-248.65 Biotechnology Research Article Research Paper |
Zdroj: | Bioengineered article-version (VoR) Version of Record Bioengineered, Vol 12, Iss 2, Pp 9367-9376 (2021) |
ISSN: | 2165-5987 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |