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Irbesartan has a curative effect on lipopolysaccharide-induced cardiotoxicity by antioxidant and antiapoptotic

Muhammet Yusuf Tepebaşi1, Halil Aşci2, Samet Coşan2

  • 1Department of Medical Genetics, University of Süleyman Demirel, Isparta, TR, Turkey.

Revista Portuguesa De Cardiologia : Orgao Oficial Da Sociedade Portuguesa De Cardiologia = Portuguese Journal of Cardiology : an Official Journal of the Portuguese Society of Cardiology
|June 29, 2023
PubMed

Insights

Irbesartan (IRB) treatment improved heart function in rats exposed to lipopolysaccharide (LPS)-induced sepsis. IRB mitigated myocardial damage, oxidative stress, and apoptosis, suggesting a protective effect against LPS cardiotoxicity.

Area of Science:

  • Cardiology
  • Pharmacology
  • Toxicology

Background:

  • Lipopolysaccharide (LPS) induces myocardial inflammation, oxidative stress, apoptosis, and cardiac dysfunction, leading to sepsis and potential death.
  • Angiotensin receptor antagonists, like irbesartan (IRB), are investigated for their potential to counteract LPS-induced cardiotoxicity.

Purpose of the Study:

  • To investigate the protective effects of irbesartan (IRB) against lipopolysaccharide (LPS)-induced cardiotoxicity.
  • To evaluate the impact of IRB on oxidative stress, apoptosis, and cardiac dysfunction markers in an LPS-induced sepsis model.

Main Methods:

  • Wistar albino rats were divided into control, LPS-only, and LPS+IRB groups.
  • Assessed oxidative stress markers (total oxidative status, total antioxidant status, oxidative stress index, ischemia-modified albumin) in serum and heart tissue.
  • Measured cardiac enzyme levels (CK, CK-MB, LDH) and analyzed mRNA expression of apoptosis-related genes (Bcl-2, BAX, p53, caspase-3) and sirtuin 1.
  • Conducted immunohistochemistry and histopathological examination of heart and aorta tissues.

Main Results:

  • LPS administration significantly increased markers of heart damage, oxidative stress, and apoptosis.
  • IRB treatment in LPS-exposed rats showed improvement in all measured parameters, indicating reduced heart damage.
  • IRB effectively counteracted the detrimental effects of LPS on cardiac oxidative stress and apoptotic pathways.

Conclusions:

  • Irbesartan (IRB) demonstrates a significant ameliorating effect on myocardial damage induced by LPS-related sepsis.
  • IRB mitigates LPS-induced cardiotoxicity by reducing oxidative stress and apoptosis in the heart.
  • The findings suggest IRB as a potential therapeutic agent for managing LPS-induced cardiac complications.
Abstract

Keywords:
ApoptoseApoptosisCardiotoxicidadeCardiotoxicityIrbesartanOxidative stressSepsisStress oxidativoSépsis

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