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Published on: January 10, 2025

Modulation of ET1/NF-κB/IL-6/STAT-4/AP-1 pathway by ambrisentan alleviates isoprenaline-induced myocardial injury

Marwa Monier Mahmoud Refaie1,2, Dina Ali Maher Abdel Dayem2,3, Olivia N Beshay4

  • 1Department of Medical Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt.

Immunopharmacology and Immunotoxicology
|May 15, 2026
PubMed

Insights

Ambrisentan (AMB) mitigated isoprenaline (ISO)-induced myocardial injury in rats. AMB demonstrated protective effects against cardiac damage, reducing enzyme levels and improving oxidative stress markers.

Area of Science:

  • Cardiology
  • Pharmacology
  • Toxicology

Background:

  • Myocardial injury is a leading cause of cardiac morbidity and mortality globally.
  • Currently, no definitive treatments exist to fully restore heart muscle function after injury.
  • This study investigated ambrisentan's potential protective role against experimentally induced myocardial damage.

Purpose of the Study:

  • To evaluate the efficacy of ambrisentan (AMB) in preventing or reducing myocardial injury induced by a toxic dose of isoprenaline (ISO).
  • To explore the underlying mechanisms of ambrisentan's cardioprotective effects.

Main Methods:

  • Rats were subjected to isoprenaline (ISO) administration to induce myocardial damage.
  • Experimental groups received varying doses of ambrisentan (AMB) concurrently with ISO.
  • Biochemical markers (cardiac enzymes, oxidative stress), histopathological changes, and specific signaling pathways were assessed.

Main Results:

  • Isoprenaline induced significant cardiac injury, evidenced by elevated cardiac enzymes (LDH, troponin I, CK-MB) and oxidative stress markers (increased MDA, decreased GSH and TAC).
  • Histopathological examination revealed toxic changes in heart tissue.
  • Co-administration of ambrisentan ameliorated these biochemical and histological alterations induced by ISO.

Conclusions:

  • Ambrisentan effectively reduced isoprenaline-induced myocardial injury in a rat model.
  • The cardioprotective effects are attributed to ambrisentan's selective endothelin A receptor antagonism.
  • Modulation of the ET-1/NF-κB/IL-6/STAT-4/AP-1 pathway contributes to ambrisentan's anti-inflammatory, anti-apoptotic, and antioxidant properties.
Abstract

Keywords:
Ambrisentanendothelinisoprenalinemyocardial injuryp-STAT-4

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