Bergapten mediated inflammatory and apoptosis through AMPK/eNOS/AKT signaling pathway of isoproterenol-induced myocardial infarction in Wistar rats

J Biochem Mol Toxicol. 2022 Sep;36(9):e23143. doi: 10.1002/jbt.23143. Epub 2022 Jul 11.

Abstract

Bergapten (BeG) is explored for its anti-inflammatory and antioxidant properties. Myocardial infarction (MI) is reported to be one of the leading cardiovascular diseases characterized by mitochondrial dysfunction and apoptosis. The main purpose of this study is to assess the cardiopreventive effects of BeG (50 mg/kg) in isoproterenol (ISO)-induced MI in Wistar rats. The increased infarct size after ISO induction was reduced simultaneously on treatment with BeG. Similarly, augmented levels of cardiac biomarkers, namely cardiac troponin T, creatine kinase (CK), cardiac troponin I, and CK-MB were also suppressed by BeG. The increased rate of lipid hydroperoxides and thiobarbituric acid reactive substances owing to the oxidative stress caused by free radical generation in ISO-induced rats were also inhibited by BeG. Antioxidants reduce oxidative stress by scavenging free radicals. ISO induction reduces these antioxidant enzymes glutathione peroxidase, catalase, superoxide dismutase, and glutathione, and levels causing oxidative cardiac damage to the heart tissue. BeG supplementation improved these enzymes synthesis preventing potential damage to the myocardium. Inflammation caused by ISO pretreatment increased the secretion of proinflammatory cytokines in ISO-induced rats. Pretreatment with BeG suppressed these inflammatory cytokines to a normal level in ISO + BeG-treated rats. The histopathological examination of the morphological characteristics showed that the intensity of cardiac damage caused by ISO induction was less in BeG pretreated rats with less inflammatory cells and no necrosis. BeG also showed promising results in the molecular alteration of AMP-activated protein kinase/endothelial nitric oxide synthase/protein kinase B signaling molecules. These observations emphasize the cardioprotective effects of BeG and its potential use as a drug in the near future.

Keywords: apoptosis; bergapten; cardiac ischemia; isoproterenol; mitochondrial dysfunction; necrosis.

MeSH terms

  • 5-Methoxypsoralen / adverse effects
  • AMP-Activated Protein Kinases* / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / therapeutic use
  • Apoptosis
  • Biomarkers / metabolism
  • Catalase / metabolism
  • Creatine Kinase, MB Form
  • Cytokines / metabolism
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Isoproterenol / toxicity
  • Lipid Peroxides / metabolism
  • Myocardial Infarction* / chemically induced
  • Myocardial Infarction* / drug therapy
  • Myocardial Infarction* / pathology
  • Myocardium / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Superoxide Dismutase / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Troponin I / adverse effects
  • Troponin I / metabolism
  • Troponin T / metabolism
  • Troponin T / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Biomarkers
  • Cytokines
  • Lipid Peroxides
  • Thiobarbituric Acid Reactive Substances
  • Troponin I
  • Troponin T
  • 5-Methoxypsoralen
  • Catalase
  • Glutathione Peroxidase
  • Nitric Oxide Synthase Type III
  • Superoxide Dismutase
  • Proto-Oncogene Proteins c-akt
  • AMP-Activated Protein Kinases
  • Creatine Kinase, MB Form
  • Glutathione
  • Isoproterenol