Melatonin, mitochondria and hypertension

Baltatu, Ovidiu Constantin; Amaral, Fernanda Gaspar do; Campos, Luciana Aparecida; Cipolla‐Neto, José

doi:10.1007/s00018-017-2613-y

Cited by 53 publications

(40 citation statements)

References 143 publications

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“…Presumably, both because of their ability to uptake [ 99 ], as well as to synthesize [ 102 ], melatonin, the mitochondria contain sufficiently high concentrations of the indole to resist the mitochondrial melee initiated by ROS. There are numerous experimental data documenting melatonin’s ability to defer mitochondrial mutilation and dysfunction resulting from the excessive production of ROS due to the inefficient transfer of electrons between the respiratory complexes [ 84 , 125 , 128 , 130 , 144 , 153 , 187 , 188 , 189 , 190 , 191 , 192 ]. Melatonin likely achieves its protective effects because of its scavenging activities, as well as those of its metabolites [ 14 , 15 , 30 , 46 , 47 , 68 , 71 ], in addition to its indirect actions in the activation of mitochondria-located SOD2; in this case, melatonin stimulates SIRT3 activity, which prompts the deacetylation and activation of SOD2, thereby reducing the oxidative burden of the mitochondria [ 126 ].…”

Section: Melatonin Oxidative Stress and Agingmentioning

confidence: 99%

Mitochondria: Central Organelles for Melatonin′s Antioxidant and Anti-Aging Actions

et al. 2018

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Melatonin, along with its metabolites, have long been known to significantly reduce the oxidative stress burden of aging cells or cells exposed to toxins. Oxidative damage is a result of free radicals produced in cells, especially in mitochondria. When measured, melatonin, a potent antioxidant, was found to be in higher concentrations in mitochondria than in other organelles or subcellular locations. Recent evidence indicates that mitochondrial membranes possess transporters that aid in the rapid uptake of melatonin by these organelles against a gradient. Moreover, we predicted several years ago that, because of their origin from melatonin-producing bacteria, mitochondria likely also synthesize melatonin. Data accumulated within the last year supports this prediction. A high content of melatonin in mitochondria would be fortuitous, since these organelles produce an abundance of free radicals. Thus, melatonin is optimally positioned to scavenge the radicals and reduce the degree of oxidative damage. In light of the “free radical theory of aging”, including all of its iterations, high melatonin levels in mitochondria would be expected to protect against age-related organismal decline. Also, there are many age-associated diseases that have, as a contributing factor, free radical damage. These multiple diseases may likely be deferred in their onset or progression if mitochondrial levels of melatonin can be maintained into advanced age.

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Section: Melatonin Oxidative Stress and Agingmentioning

confidence: 99%

Mitochondria: Central Organelles for Melatonin′s Antioxidant and Anti-Aging Actions

et al. 2018

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“…Melatonin, produced by the pineal gland, following a circadian rhythmic profile peaking during the night, is considered as a major hormone regulating the circadian rhythmicity of biological systems (1,2). Melatonin has been implicated in several regulatory functions of the cardiovascular system (3,4). Accumulating evidence indicates that melatonin plays a protective role in various cardiovascular diseases (5), mainly due to its antioxidative, antiapoptotic, and anti-inflammatory actions (6).…”

Section: Introductionmentioning

confidence: 99%

Melatonin Therapy Improves Cardiac Autonomic Modulation in Pinealectomized Patients

Campos¹,

Bueno

Barcelos

et al. 2020

Front. Endocrinol.

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The purpose of this investigational study was to assess the effects of melatonin replacement therapy on cardiac autonomic modulation in pinealectomized patients. This was an open-label, single-arm, single-center, proof-of-concept study consisting of a screening period, a 3-month treatment period with melatonin (3 mg/day), and a 6-month washout period. The cardiac autonomic function was determined through heart rate variability (HRV) measures during polysomnography. Pinealectomized patients (n = 5) with confirmed absence of melatonin were included in this study. Melatonin treatment increased vagal-dominated HRV indices including root mean square of the successive R-R interval differences (RMSSD) (39.7 ms, 95% CI 2.0-77.4, p = 0.04), percentage of successive R-R intervals that differ by more than 50 ms (pNN50) (17.1%, 95% CI 9.1-25.1, p = 0.003), absolute power of the high-frequency band (HF power) (1,390 ms 2 , 95% CI 511.9-2,267, p = 0.01), and sympathetic HRV indices like standard deviation of normal R-R wave interval (SDNN) (57.6 ms, 95% CI 15.2-100.0, p = 0.02), and absolute power of the low-frequency band (LF power) (4,592 ms 2 , 95% CI 895.6-8,288, p = 0.03). These HRV indices returned to pretreatment values when melatonin treatment was discontinued. The HRV entropy-based regularity parameters were not altered in this study, suggesting that there were no significant alterations of the REM-NREM ratios between the time stages of the study. These data show that 3 months of melatonin treatment may induce an improvement in cardiac autonomic modulation in melatonin-non-proficient patients. ClinicalTrials.gov Identifier: NCT03885258.

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“…Melatonin ( N -acetyl-5-methoxytryptamine), the main product of the pineal gland, is a pleiotropic antioxidant and anti-inflammatory indoleamine with cardioprotective properties [ 29 , 30 ]. This lipophilic indoleamine easily crosses biological membranes and resides in mitochondria, where it prevents inner membrane alterations and inhibits permeability transition pore opening [ 31 , 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Melatonin Efficacy in Obese Leptin-Deficient Mice Heart

et al. 2017

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Cardiomyocytes are particularly sensitive to oxidative damage due to the link between mitochondria and sarcoplasmic reticulum necessary for calcium flux and contraction. Melatonin, important indoleamine secreted by the pineal gland during darkness, also has important cardioprotective properties. We designed the present study to define morphological and ultrastructural changes in cardiomyocytes and mainly in mitochondria of an animal model of obesity (ob/ob mice), when treated orally or not with melatonin at 100 mg/kg/day for 8 weeks (from 5 up to 13 week of life). We observed that ob/ob mice mitochondria in sub-sarcolemmal and inter-myofibrillar compartments are often devoid of cristae with an abnormally large size, which are called mega-mitochondria. Moreover, in ob/ob mice the hypertrophic cardiomyocytes expressed high level of 4hydroxy-2-nonenal (4HNE), a marker of lipid peroxidation but scarce degree of mitofusin2, indicative of mitochondrial sufferance. Melatonin oral supplementation in ob/ob mice restores mitochondrial cristae, enhances mitofusin2 expression and minimizes 4HNE and p62/SQSTM1, an index of aberrant autophagic flux. At pericardial fat level, adipose tissue depot strictly associated with myocardium infarction, melatonin reduces adipocyte hypertrophy and inversely regulates 4HNE and adiponectin expressions. In summary, melatonin might represent a safe dietary adjuvant to hamper cardiac mitochondria remodeling and the hypoxic status that occur in pre-diabetic obese mice at 13 weeks of life.

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Melatonin, mitochondria and hypertension

Cited by 53 publications

References 143 publications

Mitochondria: Central Organelles for Melatonin′s Antioxidant and Anti-Aging Actions

Mitochondria: Central Organelles for Melatonin′s Antioxidant and Anti-Aging Actions

Melatonin Therapy Improves Cardiac Autonomic Modulation in Pinealectomized Patients

Melatonin Efficacy in Obese Leptin-Deficient Mice Heart

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