Effect of Melatonin on Rat Heart Mitochondria in Acute Heart Failure in Aged Rats.

Abstract

Excessive generation of reactive oxygen species (ROS) in mitochondria and the opening of the nonselective mitochondrial permeability transition pore are important factors that promote cardiac pathologies and dysfunction. The hormone melatonin (MEL) is known to improve the functional state of mitochondria via an antioxidant effect. Here, the effect of MEL administration on heart mitochondria from aged rats with acute cardiac failure caused by isoprenaline hydrochloride (ISO) was studied. A histological analysis revealed that chronic intake of MEL diminished the age-dependent changes in the structure of muscle fibers of the left ventricle, muscle fiber swelling, and injury zones characteristic of acute cardiac failure caused by ISO. In acute heart failure, the respiratory control index (RCI) and the Ca2+ retention capacity in isolated rat heart mitochondria (RHM) were reduced by 30% and 40%, respectively, and mitochondrial swelling increased by 34%. MEL administration abolished the effect of ISO. MEL partially prevented ISO-induced changes at the subunit level of respiratory complexes III and V and drastically decreased the expression of complex I subunit NDUFB8 both in control RHM and in RHM treated with ISO, which led to the inhibition of ROS production. MEL prevents the mitochondrial dysfunction associated with heart failure caused by ISO. It was shown that the level of 2′,3′-cyclicnucleotide-3′-phosphodiasterase (CNPase), which is capable of protecting cells in aging, increased in acute heart failure. MEL also retained the CNPase content in RHM both in control experiments and after ISO-induced heart damage. We concluded that an increase in the CNPase level promotes cardioprotection.

• Authors: Irina Odinokova, Yulia Baburina, Alexey Kruglov, Irina Fadeeva, Alena Zvyagina, Linda Sotnikova, Vladimir Akatov, Olga Krestinina
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 19 Issue 6 (05 23 2018) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 29882895 (Publication Type: Journal Article)

Chemical References

• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• Reactive Oxygen Species
• Voltage-Dependent Anion Channels
• 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase
• Melatonin
• Isoproterenol
• Calcium

Topics

• 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase (metabolism)
• Aging (pathology)
• Animals
• Calcium (metabolism)
• Cell Respiration (drug effects)
• Cryoultramicrotomy
• Electron Transport (drug effects)
• Heart Failure (metabolism, pathology)
• Heart Ventricles (pathology)
• Isoproterenol (pharmacology)
• Male
• Melatonin (pharmacology)
• Mitochondria, Heart (drug effects, metabolism)
• Mitochondrial Membrane Transport Proteins (metabolism)
• Mitochondrial Permeability Transition Pore
• Mitochondrial Swelling (drug effects)
• Rats, Wistar
• Reactive Oxygen Species (metabolism)
• Voltage-Dependent Anion Channels (metabolism)