title: Mycophenolate mofetil attenuates myocardial ischemia-reperfusion injury via regulation of the TLR4/NF-κB signaling pathway.
abstract: It has been well documented that the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway mediates early inflammatory responses during myocardial ischemia and reperfusion (MI/R). Mycophenolate mofetil (MMF), an immunosuppressive agent, has been shown to confer protective effects against ischemia/reperfusion injury, possibly through its immunosuppressive and anti-inflammatory actions. The aim of the present study was to investigate whether MMF could modulate the TLR4/NF-κB signaling, inhibit cell apoptosis and subsequently attenuate MI/R injury. MMF (20 mg/kg) or vehicle was administered to SD rats by gavage. The rats were then subjected to MI/R injury. The results showed that after MI/R, the expressions of myocardial TLR4 and NF-κB were significantly increased, and apoptosis of cardiomyocytes was induced, as evidenced by the decreased mitochondrial membrane potential (MMP), decreased Bcl-2 protein level, and increased Bax expression. Administration of MMF attenuated MI/R injury. Further studies demonstrated that MMF inhibited the induction of TLR4, NF-κB and Bax expression, and restored the expression of bcl-2. Moreover, increased myeloperoxidase activity and serum level of tumor necrotic factor α induced by MI/R injury were also inhibited by MMF treatment. In conclusion, our results demonstrated that MMF attenuates MI/R injury through inhibition of the TLR4/NF-κB signaling pathway, which led to reduced inflammatory reaction and subsequently myocardial cell apoptosis.
authors.forename: Tiecheng
authors.initials: T
authors.lastname: Li
authors.forename: Jingui
authors.initials: J
authors.lastname: Yu
authors.forename: Rongying
authors.initials: R
authors.lastname: Chen
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wu
authors.forename: Jianchun
authors.initials: J
authors.lastname: Fei
authors.forename: Qiyu
authors.initials: Q
authors.lastname: Bo
authors.forename: Ling
authors.initials: L
authors.lastname: Xue
authors.forename: Desheng
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects; D016328:NF-kappa B / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D007166:Immunosuppressive Agents; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D051197:Toll-Like Receptor 4; D051028:bcl-2-Associated X Protein; D009173:Mycophenolic Acid