Beneficial effects of benfotiamine, a NADPH oxidase inhibitor, in isoproterenol-induced myocardial infarction in rats

PLoS One. 2020 May 8;15(5):e0232413. doi: 10.1371/journal.pone.0232413. eCollection 2020.

Abstract

Background: Acute myocardial infarction (AMI) remains the most common cause of morbidity and mortality worldwide. The present study was directed to investigate the beneficial effects of benfotiamine pre- and post-treatments in isoproterenol (ISO)-induced MI in rats.

Methods: Myocardial heart damage was induced by subcutaneous injection of ISO (150 mg/kg) once daily for two consecutive days. Benfotiamine (100 mg/kg/day) was given orally for two weeks before or after ISO treatment.

Results: ISO administration revealed significant changes in electrocardiographic recordings, elevation of levels of cardiac enzymes; creatinine kinase (CK-MB) and troponin-I (cTn-I), and perturbation of markers of oxidative stress; nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) and markers of inflammation; protein kinase C (PKC), nuclear factor-kappa B (NF-κB) and metalloproteinase-9 (MMP-9). The apoptotic markers (caspase-8 and p53) were also significantly elevated in ISO groups in addition to histological alterations. Groups treated with benfotiamine pre- and post-ISO administration showed significantly decreased cardiac enzymes levels and improved oxidative stress, inflammatory and apoptotic markers compared to the ISO groups.

Conclusion: The current study highlights the potential role of benfotiamine as a promising agent for prophylactic and therapeutic interventions in myocardial damage in several cardiovascular disorders via NADPH oxidase inhibition.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cardiotoxins / toxicity
  • Disease Models, Animal
  • Electrocardiography
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Inflammation Mediators / metabolism
  • Isoproterenol / toxicity
  • Male
  • Myocardial Infarction / chemically induced
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism
  • Myocardium / metabolism
  • Myocardium / pathology
  • NADPH Oxidases / antagonists & inhibitors*
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Thiamine / analogs & derivatives*
  • Thiamine / therapeutic use

Substances

  • Biomarkers
  • Cardiotoxins
  • Enzyme Inhibitors
  • Inflammation Mediators
  • NADPH Oxidases
  • Isoproterenol
  • Thiamine
  • benphothiamine

Grants and funding

The authors received no specific funding for this work.