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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Animals, Biomarkers, Cytokines, Disaccharides, Drug Evaluation, Preclinical, Enzyme Activation, Inflammation, JNK Mitogen-Activated Protein Kinases, Male, Mice, Mice, Inbred C57BL, Mitogen-Activated Protein Kinases, Myocardial Infarction, Myocardial Reperfusion Injury, NF-kappa B, Phosphorylation, Protein Processing, Post-Translational, Sugar Phosphates, Toll-Like Receptor 4.
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Does inhibition of Toll-like receptor 4 with eritoran attenuate myocardial ischemia-reperfusion injury? Context: We previously reported that the functional mutation of Toll-like receptor 4 (TLR4) in C3H/HeJ mice subjected to myocardial ischemia-reperfusion (MI/R) injury resulted in an attenuation of myocardial infarction size. To investigate the ligand-activating TLR4 during MI/R injury, we evaluated the effect of eritoran, a specific TLR4 antagonist, on MI/R injury, with the goal of defining better therapeutic options for MI/R injury. C57BL/6 mice received eritoran (5 mg/kg) intravenously 10 minutes before 30 minutes of in situ of transient occlusion of the left anterior descending artery, followed by 120 minutes of reperfusion. Infarct size was measured using triphenyltetrazoliumchloride staining. A c-Jun NH(2)-terminal kinase (JNK) activation was determined by Western blotting, nuclear factor (NF)-kappaB activity was detected by gel-shift assay, and cytokine expression was measured by ribonuclease protection assay. Mice treated with eritoran developed significantly smaller infarcts when compared with mice treated with vehicle alone (21.0+/-6.4% versus 30.9+/-13.9%; P=0.041). Eritoran pretreatment resulted in a reduction in JNK phosphorylation (eritoran versus vehicle: 3.98+/-0.81 versus 7.01+/-2.21-fold increase; P=0.020), less nuclear NF-kappaB translocation (2.70+/-0.35 versus 7.75+/-0.60-fold increase; P=0.00007), and a decrease in cytokine expression (P<0.05).
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We conclude that inhibition of TLR4 with eritoran in an in situ murine model significantly reduces MI/R injury and markers of an inflammatory response. Final Decision: yes