Oleic acid ameliorates adrenaline induced dysfunction of rat heart mitochondria by binding with adrenaline: An isothermal titration calorimetry study

Life Sci. 2019 Feb 1:218:96-111. doi: 10.1016/j.lfs.2018.12.035. Epub 2018 Dec 20.

Abstract

Aims: Our earlier studies revealed the cardio-protective effects of oleic acid, a monounsaturated fatty acid, against adrenaline induced myocardial injury. Moreover, it has been found to possess antioxidant properties. Thus, in the present study we have investigated the protective role of oleic acid on adrenaline induced mitochondrial dysfunction in vitro in rat heart mitochondria.

Main methods: Isolated rat cardiac mitochondria was incubated in vitro with adrenaline-bitartrate alone and with graded doses of oleic acid. Biomarkers of oxidative stress, mitochondrial Krebs cycle enzymes and respiratory chain enzymes along with mitochondrial morphology, membrane potential as well as intactness were analyzed. Isothermal titration calorimetric studies with pure adrenaline and oleic acid was also carried out.

Key findings: Incubation with adrenaline, in vitro, showed elevated levels of lipid peroxidation and protein carbonylation of mitochondrial membrane, a reduced level of glutathione content along with an altered profile of mitochondrial enzymes, morphology, membrane potential as well as intactness. All these changes were found to be ameliorated when cardiac mitochondria were co-incubated with adrenaline and oleic acid, in vitro.

Significance: Our earlier studies demonstrated the antioxidant properties of oleic acid. This study suggests that oleic acid binds adrenaline with high affinity gradual saturation of the binding sites of adrenaline. This prevents the generation of ROS and finally providing consequent protection of the cardiac mitochondria and ameliorating adrenaline induced mitochondrial dysfunction. Hence, oleic acid may be considered as a potent future cardio-protective antioxidant.

Keywords: Adrenaline; Antioxidant; Heart mitochondria; Oleic acid; Oxidative stress.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Calorimetry / methods*
  • Cells, Cultured
  • Epinephrine / metabolism*
  • Epinephrine / toxicity*
  • Heart Diseases / chemically induced
  • Heart Diseases / metabolism
  • Heart Diseases / pathology*
  • Male
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / metabolism
  • Mitochondria, Heart / pathology
  • Oleic Acid / pharmacology*
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Vasoconstrictor Agents / metabolism
  • Vasoconstrictor Agents / toxicity

Substances

  • Antioxidants
  • Vasoconstrictor Agents
  • Oleic Acid
  • Epinephrine