Melatonin actions in the heart; more than a hormone

Melatonin and heart

  • Darío Acuña-Castroviejo Centro de Investigación Biomédica, Departamento de Fisiología, Facultad de Medicina, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain; CIBERfes, Ibs.Granada, Unidad de Gestión Clínica de Laboratorios Clínicos, Complejo Hospitalario de Granada, Granada, Spain
  • Maria T Noguiera-Navarro Centro de Investigación Biomédica, Departamento de Fisiología, Facultad de Medicina, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain
  • Russel J Reiter Department of Cell Systems and Anatomy, The University of Texas, Health, San Antonio, USA
  • Germaine Escames Centro de Investigación Biomédica, Departamento de Fisiología, Facultad de Medicina, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain; CIBERfes, Ibs.Granada, Unidad de Gestión Clínica de Laboratorios Clínicos, Complejo Hospitalario de Granada, Granada, Spain
DOI: https://doi.org/10.32794/mr11250002
Keywords: melatonin; heart; subcellular distribution; pinealectomy

Abstract

Due to the broad distribution of extrapineal melatonin in multiple organs and tissues, we analyzed the presence and subcellular distribution of the indoleamine in the heart of rats. Groups of sham-operated and pinealectomized rats were sacrificed at different times along the day, and the melatonin content in myocardial cell membranes, cytosol, nuclei and mitochondria, were measured. Other groups of control animals were treated with different doses of melatonin to monitor its intracellular distribution. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and mitochondria vary along the day, without showing a circadian rhythm. Pinealectomized animals trend to show higher values than sham-operated rats. Exogenous administration of melatonin yields its accumulation in a dose-dependent manner in all subcellular compartments analyzed, with maximal concentrations found in cell membranes at doses of 200 mg/kg bw melatonin. Interestingly, at dose of 40 mg/kg b.w, maximal concentration of melatonin was reached in the nucleus and mitochondrion. The results confirm previous data in other rat tissues including liver and brain, and support that melatonin is not uniformly distributed in the cell, whereas high doses of melatonin may be required for therapeutic purposes.

Author Biography

Darío Acuña-Castroviejo, Centro de Investigación Biomédica, Departamento de Fisiología, Facultad de Medicina, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain; CIBERfes, Ibs.Granada, Unidad de Gestión Clínica de Laboratorios Clínicos, Complejo Hospitalario de Granada, Granada, Spain

Prof. Acuña-Castroviejo received his MD degree in 1975 and his PhD in 1977 from the University of Granada. This was followed by a postdoctoral research at the CONICET (Centro de Estudios Farmacológicos y de Principios Naturales, Buenos Aires, Argentina (Prof. Daniel P Cardinali), and at the HT Science Center, University of Texas, USA (Prof. Russel J Reiter). He was a recipient of fellowships from the University of Granada and the Spanish Ministry of Education. He joined University of Granada in 1983 and is currently a Full Professor in Physiology at the Granada School of Medicine. He is also MD specialized in Clinical Analysis, and Director of the Free Radical’s Laboratory, Biopathology Laboratory, San Cecilio’s University Hospital, Granada, Spain. Prof. Acuña is Group leader in Neuroendocrinology investigating the mechanisms of action of melatonin and its clinical application in aging, sepsis, and neurodegenerative diseases. He published key articles on the nuclear receptor of melatonin; its role on mitochondrial homeostasis; and the anti-parkinsonian and anti-septic properties of melatonin.  Prof. Acuña worked of the experimental models of sepsis in mice and rats that allowed the development of the patent of an injectable melatonin. He has a number of patents on melatonin and its derivatives, including their application in sepsis, mucositis, and skin regeneration, and participated in the clinical trial with the injectable melatonin in sepsis. Moreover, Prof. Acuña constituted two I+D Spin-off of the University of Granada devoted to the development of two of these patents (Pharmamel, S.L., e Inymel Biomédica, S.L.). Over 300 publications support the large experience of Prof. Acuña on melatonin research, which enables him an opinion leader in the field of basic and clinical applications of melatonin.

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Published
2018-12-03
How to Cite
[1]
Acuña-Castroviejo, D., Noguiera-Navarro, M., Reiter, R. and Escames, G. 2018. Melatonin actions in the heart; more than a hormone. Melatonin Research. 1, 1 (Dec. 2018), 21-26. DOI:https://doi.org/https://doi.org/10.32794/mr11250002.
Issue
Vol 1 No 1 (2018): Inaugural Issue of Melatonin Research
Section
Research Articles
DOI
https://doi.org/10.32794/mr11250002
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