Cardioprotective Effects of Eritoran During Polymicrobial Sepsis Through Decreases of p38MAPK/NF-κB Signaling Pathway

18 Pages Posted: 26 Mar 2019

See all articles by Nasser Yousif

Nasser Yousif

Al Muthanna University

Najah R. Hadi

Kufa University

Qassim A. Zigam

Kufa University

Ahmed N. Altimimi

Kufa University

Date Written: March 2, 2019

Abstract

Background: Sepsis is a systemic inflammatory response usually correlates with multiorgan dysfunction. Myocardial dysfunction is one of adverse outcomes in septic patients resulted in high mortality rate. Aim: To study the impact of eritoran in attenuation of cardiac depression during polymicrobial sepsis via decreased of phospho-p38MAPK/NF-κB signaling pathway. Methods and materials: Polymicrobial sepsis induced via cecal ligation and puncture model (CLP), in 8-12 weeks' age albino mice, 1hr prior to CLP mice were treated with IP eritoran (5mg/kg). Twenty-four hours post CLP hemodynamic parameters including: heart rate, ejection fraction, LVEDP, LVSP and cardiac output, were carried out using micro-tipped transducer catheter. Plasma levels of proinflammatory cytokines, including TNF-α, IL-1β and IL-6, chemokine MCP-1 and cTn-I were measured via ELISA analysis. Phosphorylation degree of P38 MAPK and NF-κB carried out through western blot technique. Results: Mice were treated with eritoran displayed improvement of LV function (Ejection fraction: 42.4 ± 1.1% versus 27.8 ± 3% in CLP mice). The attenuation of cardiac depression in eritoran treated mice was associated with lower levels of monocyte chemoattractant protein-1 (MCP-1) in plasma, and reduction in the levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6). Furthermore, eritoran treated mice displayed less expression levels of phosphorylation p38-MAPK and NF-κB. Conclusion: eritoran can attenuate the cardiac dysfunction during polymicrobial sepsis possibly via a reduction of proinflammatory cytokines through decreased of both p38MAPK and NF-κB activation.

Keywords: Eritoran, Sepsis, p38MAPK/NF-κB, Cardioprotective

Suggested Citation

Yousif, Nasser and Hadi, Najah R. and Zigam, Qassim A. and Altimimi, Ahmed N., Cardioprotective Effects of Eritoran During Polymicrobial Sepsis Through Decreases of p38MAPK/NF-κB Signaling Pathway (March 2, 2019). Available at SSRN: https://ssrn.com/abstract=3345558 or http://dx.doi.org/10.2139/ssrn.3345558

Nasser Yousif (Contact Author)

Al Muthanna University ( email )

Iraq

Najah R. Hadi

Kufa University

Najaf
Iraq

Qassim A. Zigam

Kufa University

Najaf
Iraq

Ahmed N. Altimimi

Kufa University

Najaf
Iraq

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