Allyl Methyl Sulfide Preserved Pressure Overload-Induced Heart Failure Via Modulation of Mitochondrial Function

Biomed Pharmacother. 2021 Jun:138:111316. doi: 10.1016/j.biopha.2021.111316. Epub 2021 Mar 5.

Abstract

Background: Cardiovascular diseases are the leading cause of death globally, and they are causing enormous socio-economic burden to the developed and developing countries. Allyl Methyl Sulfide (AMS) is a novel cardioprotective metabolite identified in the serum of rats after raw garlic administration. The present study explored the cardioprotective effect of AMS on thoracic aortic constriction (TAC)-induced cardiac hypertrophy and heart failure model in rats.

Methods: Thoracic aortic constriction (TAC) by titanium ligating clips resulted in the development of pressure overload-induced cardiac hypertrophy and heart failure model. Four weeks prior to TAC and for 8 weeks after TAC, Sprague Dawley (SD) rats were administered with AMS (25 and 50 mg/kg/day) or Enalapril (10 mg/kg/day).

Results: We have observed AMS (25 and 50 mg/kg/day) intervention significantly improved structural and functional parameters of the heart. mRNA expression of fetal genes i.e., atrial natriuretic peptide (ANP), alpha skeletal actin (α-SA) and beta myosin heavy chain (β-MHC) were reduced in AMS treated TAC hearts along with decrease in perivascular and interstitial fibrosis. AMS attenuated lipid peroxidation and improved protein expression of endogenous antioxidant enzymes i.e., catalase and manganese superoxide dismutase (MnSOD) along with electron transport chain (ETC) complex activity. AMS increased mitochondrial fusion proteins i.e., mitofusin 1 (MFN1), mitofusin 2 (MFN2) and optic atrophy protein (OPA1), and reduced fission protein i.e., dynamin-related protein 1 (DRP1). Preliminary study suggests that AMS intervention upregulated genes involved in mitochondrial bioenergetics in normal rats. Further, in-vitro studies suggest that AMS reduced mitochondrial reactive oxygen species (ROS), preserved mitochondrial membrane potential and oxygen consumption rate (OCR) in isoproterenol-treated cardiomyoblast.

Conclusion: This study demonstrated that AMS protected cardiac remodelling, LV dysfunction and fibrosis in pressure overload-induced cardiac hypertrophy and heart failure model by improving endogenous antioxidants and mitochondrial function.

Keywords: Allyl Methyl Sulfide; Heart failure; Metabolite; Mitochondrial dynamics; Thoracic aortic constriction.

MeSH terms

  • Allyl Compounds / pharmacology
  • Allyl Compounds / therapeutic use*
  • Animals
  • Aorta, Thoracic / diagnostic imaging
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiopathology
  • Cardiomegaly / diagnostic imaging
  • Cardiomegaly / drug therapy
  • Cardiomegaly / physiopathology
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Cell Line
  • Heart Failure / diagnostic imaging
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Male
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Stroke Volume / drug effects
  • Stroke Volume / physiology
  • Sulfides / pharmacology
  • Sulfides / therapeutic use*

Substances

  • Allyl Compounds
  • Cardiotonic Agents
  • Sulfides
  • allyl methyl sulfide