DigitalUM :: Browsing by Subject "Melatonin"

Browsing by Subject "Melatonin"

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Open Access
An in vitro study on the effects of melatonin on the ultrastructure of the hamster parathyroid gland
(Murcia : F. Hernández, 1992) shoumura, S.; chen, H.; Emura, S.; Utsumi, M.; Hayakawa, D.; Yamahira, T.; Terasawa, K.; Tamada, A.; Arakawa, M.; Isono, H.
Isolated parathyroid glands from adult female golden hamsters were incubated on a black Millipore filter in an incubation vessel containing Ham's F-12 medium, with or without melatonin at final concentration of 10-5 M for 1 hour. In the parathyroid glands used for in vitro treatments with melatonin, the Golgi complexes associated with a few prosecretory granules and cisternae of the rough endoplasmic reticulum showed a significant decrease, and lipid droplets and lysosomes appeared to be increased compared with those of the control parathyroid glands. These changes are considered to be induced by suppression of the synthesis of parathyroid hormone in parathyroid glands incubated in a vessel containing medium with melatonin.
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Circadian phase asessment by ambulatory monitoring in humans: correlation with dim light melatonin onset
(Taylor and Francis Group, 2013-10-28) Middleton, Benita; Revell, Victoria L.; Skene, Debra J.; Rol, Maria-Angeles; Madrid, Juan Antonio; Bonmatí Carrión, María de los Ángeles; Anatomía Humana y Psicobiología
The increased prevalence of circadian disruptions due to abnormal coupling between internal and external time makes the detection of circadian phase in humans by ambulatory recordings a compelling need. Here, we propose an accurate practical procedure to estimate circadian phase with the least possible burden for the subject, that is, without the restraints of a constant routine protocol or laboratory techniques such as melatonin quantification, both of which are standard procedures. In this validation study, subjects (N = 13) wore ambulatory monitoring devices, kept daily sleep diaries and went about their daily routine for 10 days. The devices measured skin temperature at wrist level (WT), motor activity and body position on the arm, and light exposure by means of a sensor placed on the chest. Dim light melatonin onset (DLMO) was used to compare and evaluate the accuracy of the ambulatory variables in assessing circadian phase. An evening increase in WT: WTOnset (WTOn) and “WT increase onset” (WTiO) was found to anticipate the evening increase in melatonin, while decreases in motor activity (Activity Offset or AcOff), body position (Position Offset (POff)), integrative TAP (a combination of WT, activity and body position) (TAPOffset or TAPOff) and an increase in declared sleep propensity were phase delayed with respect to DLMO. The phase markers obtained from subjective sleep (R = 0.811), WT (R = 0.756) and the composite variable TAP (R = 0.720) were highly and significantly correlated with DLMO. The findings strongly support a new method to calculate circadian phase based on WT (WTiO) that accurately predicts and shows a temporal association with DLMO. WTiO is especially recommended due to its simplicity and applicability to clinical use under conditions where knowing endogenous circadian phase is important, such as in cancer chronotherapy and light therapy.
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Circadian system functionality, hippocampal oxidative stress, and spatial memory in the APPswe/PS1dE9 transgenic model of Alzheimer disease: effects of melatonin or ramelteon
(Taylor and Francis Group, Taylor and Francis, 2012-07-23) Baño-Otalora, Beatriz; Gambini, Juan; Viña, José; Bonet-Costa, Vicent; Reiter, Russel J.; Camello, Pedro Javier; Rol, María Ángeles; Madrid, Juan Antonio; Popovic, Natalija; Popovic Popovic, Miroljub; Anatomía Humana y Psicobiología
Alzheimer disease (AD) is a neurodegenerative disorder that primarily causes β-amyloid accumulation in the brain, resulting in cognitive and behavioral deficits. AD patients, however, also suffer from severe circadian rhythm disruptions, and the underlying causes are still not fully known. Patients with AD show reduced systemic melatonin levels. This may contribute to their symptoms, since melatonin is an effective chronobiotic and antioxidant with neuroprotective properties. Here, the authors critically assessed the effects of long-term melatonin treatment on circadian system function, hippocampal oxidative stress, and spatial memory performance in the APPswe/PS1 double transgenic (Tg) mouse model of AD. To test if melatonin MT1/MT2 receptor activation, alone, was involved, the authors chronically treated some mice with the selective MT1/MT2 receptor agonist ramelteon. The results indicate that many of the circadian and behavioral parameters measured, including oxidative stress markers, were not significantly affected in these AD mice. During the day, though, Tg controls (Tg-CON) showed significantly higher mean activity and body temperature (BT) than wild-type (WT) mice. Overall, BT rhythm amplitude was significantly lower in Tg than in WT mice. Although melatonin treatment had no effect, ramelteon significantly reduced the amplitude of the BT rhythm in Tg mice. Towards the end of the experiment, Tg mice treated with ramelteon (Tg-RAM) showed significantly higher circadian rhythm fragmentation than Tg-CON and reduced circadian BT rhythm strength. The free-running period (τ) for the BT and locomotor activity (LA) rhythms of Tg-CON was <24 h. Whereas melatonin maintained τ at 24 h for BT and LA in both genotypes, ramelteon treatment had no effect. In the behavioral tests, the number of approaches and time spent exploring novel objects were significantly higher in Tg-CON than WT controls. Brain tissue analysis revealed significant reduction in hippocampal protein oxidation in Tg-MEL and Tg-RAM compared with Tg-CON animals. These results suggest that not all aspects of the circadian system are affected in the APPswe/PS1 mice. Therefore, care should be taken when extending the results obtained in Tg mice to develop new therapies in humans. This study also revealed the complexity in the therapeutic actions of melatonin and ramelteon in this mouse model of AD.
Open Access
Correlated color temperature and light intensity: complementary features in non-visual light field
(Public Library of Science (PLoS), 2021-07-12) Arguelles Prieto, Raquel; Madrid, Juan Antonio; Rol de Lama, María de los Ángeles; Bonmatí Carrión, María de los Ángeles; Fisiología
An appropriate exposure to the light-dark cycle, with high irradiances during the day and darkness during the night is essential to keep our physiology on time. However, considering the increasing exposure to artificial light at night and its potential harmful effects on health (i.e. chronodisruption and associated health conditions), it is essential to understand the non-visual effects of light in humans. Melatonin suppression is considered the gold standard for nocturnal light effects, and the activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) through the assessment of pupillary light reflex (PLR) has been recently gaining attention. Also, some theoretical models for melatonin suppression and retinal photoreceptors activation have been proposed. Our aim in this study was to determine the influence of correlated color temperature (CCT) on melatonin suppression and PLR, considering two commercial light sources, as well as to explore the possible correlation between both processes. Also, the contribution of irradiance (associated to CCT) was explored through mathematical modelling on a wider range of light sources. For that, melatonin suppression and PLR were experimentally assessed on 16 healthy and young volunteers under two light conditions (warmer, CCT 3000 K; and cooler, CCT 5700 K, at ~5·1018 photons/cm2/sec). Our experimental results yielded greater post-stimulus constriction under the cooler (5700 K, 13.3 ± 1.9%) than under the warmer light (3000 K, 8.7 ± 1.2%) (p < 0.01), although no significant differences were found between both conditions in terms of melatonin suppression. Interestingly, we failed to demonstrate correlation between PLR and melatonin suppression. Although methodological limitations cannot be discarded, this could be due to the existence of different subpopulations of Type 1 ipRGCs differentially contributing to PLR and melatonin suppression, which opens the way for further research on ipRGCs projection in humans. The application of theoretical modelling suggested that CCT should not be considered separately from irradiance when designing nocturnal/diurnal illumination systems. Further experimental studies on wider ranges of CCTs and light intensities are needed to confirm these conclusions.
Open Access
Day-night changes in plasma melatonin levels, synaptophysin expression and ultrastructural properties of pinealocytes in developing female sheep under natural long and short photoperiods
(Murcia : F. Hernández, 2003) Redondo, E.; Regodón, S.; Franco, A.; Masot, A.J.; Gázquez, A.; Cardinali, D.P.
The aim of the present study was to analyze the 24-h rhythm in plasma melatonin concentration and the day-night differences in synaptophysin expresion and ultrastructural characteristics of the pinealocytes in developing female sheep. Ewes of three different ages were examined: infantile (1-6 months old), pubertal and early fertile age (9-24 months old) and adult (36-60 months old). Experiments were conducted under natural non-stimulatory (long) and stimulatory (short) photoperiods. The obtained results were similar for both analyzed photoperiods. Plasma melatonin concentration, measured in samples obtained every 4 h, showed a similar pattern in the three age groups, with peak values at 02:00 h and troughs at 14:00 h. Mean value of plasma melatonin levels in 9-24 month-old sheep was significantly greater than that in younger or older sheep. The weight of pineal glands obtained at night (02:00 h) was significantly higher than in daylight (14:00 h). Pubertal and early fertile sheep had the largest pineal glands. The pineal volume, and the total number of pinealocytes per gland of 9-24 months-old sheep differed significantly from that of younger or older sheep. The pineal volume, and the mean volume of pinealocytes was significantly greater in animals killed at night. Number of pinealocytes did not vary between animals killed during daylight or at night. The mean volumen of pinealocytes did not show statistical differences between the age groups. In quantitative ultrastructural analysis of pinealocyte cells, the relative volume of mitochondria, rough endoplasmic reticulum and Golgi complexes was significantly greater in 9-24 month-old sheep and in animals killed at night. The relative volume of lipid droplets was highest in older sheep. Collectively, the data support the existence of developmental changes in pinealocyte morphology and quantity, partially in coincidence with a higher melatonin secretion rate.
Open Access
Differential light intensity and spectral sensitivities of atlantic salmon, european sea bass and atlantic cod pineal glands ex vivo
(2010) Vera, L.M.; Davie, A.; Taylor, J.F.; Migaud, H.; Fisiología
Photoperiod is perceived by pineal photoreceptors and transduced into rhythmic melatonin signals. These rhythms can be influenced by light intensity and spectral content. In this study we compared the light sensitivity of Atlantic salmon, European sea bass and Atlantic cod by testing ex vivo the effect of different intensities and narrow bandwidth lights on nocturnal melatonin suppression by isolated pineal glands in a flow-through culture system. Using combinations of neutral density and bandpass interference filters we tested a range of light intensities (ranging from 1.22 x 1013 – 3.85 x 106 photons.s-1 .cm-2 ) and three wavelengths of 80 nm width (472, 555 and 661 nm corresponding to blue, green and red, respectively). Results showed clear species specific light intensity and spectral sensitivities, with cod being from 100 to 1000 times more sensitive than sea bass and salmon. Regarding the influence of spectrum, red light was less efficient on suppressing melatonin than blue and green in salmon but results were not as clear in the two other species studied. Finally, the first evidence of relative photoreception in teleosts was obtained in cod suggesting that the definition of illuminance thresholds (day/night perception) would depend on the day intensity. Indeed, a single order of magnitude increase or decrease in day intensity was shown to elicit a significant shift in the intensity response curve of night-time melatonin suppression. Taken together, this study demonstrated species specific light intensity and spectral sensitivities within temperate teleosts.
Open Access
Disincronía circadiana y su efecto sobre parámetros de síndrome metabólico en trabajadores: revisión integradora de la literatura
(Universidad de Murcia. Servicio de publicaciones, 2021) Zepeda Ríos, Paola Alexandra; Quintana Zavala, María Olga
Introducción: La pérdida del ritmo circadiano causado por desórdenes del sueño es considerada un factor de riesgo importante para desarrollar enfermedades metabólicas como hiperglicemia y resistencia a la insulina. Objetivo: Analizar la literatura existente referente a estudios sobre disincronía circadiana en trabajadores y su influencia sobre parámetros antropométricos de síndrome metabólico de los mismos. Método: Se realizó una búsqueda en las bases de datos electrónicas EBSCO, Thompson Reuters, PubMed y Scopus, los términos de búsqueda seleccionados fueron: trabajo por turnos, melatonina, cortisol, síndrome metabólico, trabajo nocturno y ritmo circadiano, en los idiomas español e inglés, publicados de enero del 2015 a diciembre de 2018. La extracción se llevó a cabo utilizando un formulario prediseñado. Resultados: La búsqueda en las bases de datos arrojó 5,953 artículos, posterior a la indagación y depuración de los mismos aplicando los criterios de elegibilidad, se obtuvieron 13 artículos los cuales se organizaron en dos dimensiones para su análisis, estas se denominaron a) trabajo en turnos y factores de riesgo metabólico y b) trabajo en turnos y ciclo circadiano. Conclusiones: Es consistente la relación entre el trabajo nocturno o rotatorio, con diversas alteraciones metabólicas.
Open Access
Effect of melatonin on the cardiotoxicity of doxorubicin
(Murcia : F. Hernández, 2004) Balli, E.; Mete, U.O.; Tuli, A.; Tap, O.; Kaya, M.
This study was designed to investigate the preventive effect of melatonin on doxorubicin’s most important side effect, cardiotoxicity. Forty male albino Wistar rats were utilized and the rats were divided into five groups: group I, 0.9 % NaCl for 4 days; group II, doxorubicin 3 mg/kg/day for 4 days; group III, 2.5 % ethanol for 15 days; group IV, melatonin 6 mg/kg/day for 15 days; and group V, a doxorubicin and melatonin combination were administered intraperitoneally. At the end of the experiment, tissue samples obtained from the cardiac muscle of the left ventricle of the rats were processed for measurement of malondialdehyde and for electron microscopic examination. Malondialdehyde, a product of lipid peroxidation, was found to be significantly higher in the doxorubicin group. However, in the doxorubicin and melatonin combination group the level of malondialdehyde was decreased statistical significant. The histological examination revealed destruction of myofibrils, disorganization of sarcomeres, mitochondrial degeneration and formation of giant mitochondria and lipid accumulation in the doxorubicin group. Also, accumulation of filamentous structures in the sarcoplasma in some of the cells, structural changes in capillaries and an increase in collagen fibers forming bundles were observed. When melatonin was added to the doxorubicin treatment all structural changes were reduced. The cardiotoxic side effect of doxorubicin used as a chemotherapeutic agent and was probably developed as a result of supression of the antioxidant system and lipid peroxidation. Therefore, it could be assumed that the addition of melatonin in the treatment of doxorubicin could prevent the cardiotoxicity of doxorubicin.
Open Access
Effects of melatonin on the ultrastructure of the golden hamster parathyroid gland
(Murcia : F. Hernández, 1991) Huayue Chen; Shizuko Shoumura; Shoichi Emura; Michiya Utsumi; Tomo Yamahira; Hideo Isono
Ultrastructural changes of the parathyroid glands of melatonin-treated golden hamsters were studied. Many chief cells in the parathyroid glands after 1 hour of administration of melatonin contained poorlydeveloped Golgi complexes associated with a few prosecretory granules and numerous lipid droplets as compared with those of the control animals. The morphology of the parathyroid glands after 5 hours of administration resembled that of the control animals. Many chief cells in the parathyroid glands after 24 hours of administration had well-developed Golgi complexes and cisternae of the granular endoplasmic reticulum, numerous prosecretory granules, a few lipid droplets and many secretory granules in the peripheral cytoplasm as compared with those of the control animals. The ultrastructure of the parathyroid glands after 48 hours of administration was almost similar to that of the control animals. It is considered that melatonin affects the secretory activity of the parathyroid gland.
Open Access
Effects of melatonin, testosterone and the two hormones administered in parallel on epididymis of the rat estrogenized with stilbestrol in the first day of life
(Murcia : F. Hernández, 1996) Limanowski, A.; Miskowiak, B.; Otulakowski, B.
Effect of melatonin, testosterone and of both hormones given in parallel on rat epididymis was tested in rats given a single dose of 1 mg stilbestrol on the first day of the life. The hormones were given daily for 39 days, beginning from the 20th or 28th day of life. The single dose of estrogen treatment resulted in epididymis atrophy, accompanied by changes in glandular epithelium and in its stroma, when the rats reached mature age (59 or 67 days of life). In such rats, LH gonadotropin level was elevated and testosterone level was decreased. Administration of melatonin failed to affect the changes induced by estrogen treatment. Administration of testosterone alone or of testosterone in parallel with melatonin caused the epididymis status to resemble more closely that seen in control animals. Efferent ductules of the testis (head of epididymis) were also demonstrated to be more sensitive to the performed experimental procedures than the duct of the epididymis (body and tail of the epididymis).
Open Access
Effects of water salinity on melatonin levels in plasma and peripheral tissues and on melatonin binding sites in European sea bass (Dicentrarchus labrax)
(Elsevier, 2009) López Olmeda, José Fernando; Oliveira, Catarina; Kalamarz, Hanna; Kulczykowska, Ewa; Delgado, María Jesús; Sánchez Vázquez, Francisco Javier; Fisiología
Sea bass is a euryhaline fish that lives in a wide range of salinities and migrates seasonally from lagoons to the open sea. However, to date, the influence of water salinity on sea bass melatonin levels has not been reported. Here, we evaluated the differences in plasma and tissue melatonin contents and melatonin binding sites in sea bass under four different salinities: seawater (36 ‰), isotonic water (15 ‰), brackish (4 ‰) and freshwater (0 ‰). Melatonin content was evaluated in plasma, whole brain, gills, intestine and kidney, while melatonin binding sites were analyzed in different brain regions and in the neural retina. Plasma melatonin levels at mid-dark varied among salinities, with the lowest value occurring at seawater salinity (102 pg/ml), and the highest at freshwater (151 pg/ml). In gills and intestine, however, the highest melatonin values were found in the seawater group (209 and 627 pg/g tissue, respectively). Melatonin binding sites in the brain also varied with salinity, with the highest density being observed at the lower salinities in optic tectum, cerebellum and hypothalamus (30.3, 13.0, and 8.0 fmol/mg protein, respectively). Melatonin binding sites in the retina showed a similar pattern, with the highest values in the fish maintained in freshwater. Taken together, these results revealed that salinity influences melatonin production and modifies the density of binding sites, which would point to a role for this hormone in timing seasonal events in sea bass, including those linked to fish migration between waters of different salinities.
Open Access
Feeding entrainment of locomotor activity rhythms, digestive enzymes and neuroendocrine factors in goldfish
(2007) Vera, L.M.; De Pedro, N.; Gómez Milán, E.; Delgado, M.J.; Sánchez Muros, M.J.; Madrid, J.A.; Sánchez Vázquez, F.J.; Fisiología
L.M. VERA, N. DE PEDRO, E. GÓMEZ-MILÁN, M.J. DELGADO, M.J. SÁNCHEZ MUROS, J.A. MADRID, F.J. SÁNCHEZ-VÁZQUEZ. Feeding entrainment of locomotor activity, digestive enzymes and neuroendocrine factors in goldfish. PHYSIOL BEHAV 90 (2-3) 518-524, 2007. The existence of food anticipatory activity (FAA) in animals subjected to daily feeding schedules seems to be mediated by a feeding-entrainable oscillator (FEO). Such an FEO may help in anticipating meal time and so optimizing food acquisition and nutrient utilization. In this study we investigated the existence of FAA and whether digestive enzymes, plasma cortisol, hypothalamic NPY and gastrointestinal tract (GIT) and plasma melatonin were entrained by periodic feeding in goldfish. We observed that periodically fed goldfish showed FAA in locomotor activity as well as in amylase and NPY. Alkaline protease and GIT melatonin were higher after feeding, whereas plasma cortisol levels were reduced. Plasma melatonin remained unmodified before and after meal time. These results suggested that scheduled feeding entrained both behavioral and certain physiological patterns in goldfish, FAA being of adaptive value to anticipate a meal and prepare the digestive physiology of fish.
Open Access
Histological study of the protective effect of melatonin on neural cells after neonatal hypoxia-ischemia
(F. Hernandez y JuanF. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología., 2012) Alonso-Alconada, Daniel; Álvarez, Antonia; Lacalle, J.; Hilario, Enrique
To minimize as much as possible the neurological consequences from hypoxic-ischemic (HI) brain injury, neuroprotective strategies are urgently required. In this sense, there is growing interest in the neuroprotective potential of melatonin after perinatal asphyxia, due to its high efficacy, low toxicity and ready cross through the blood-brain barrier. Twenty six Wistar rats at postnatal day 7 were randomly assigned to: two hypoxic-ischemic groups: pups with the left common carotid artery ligated and then submitted to hypoxia (HI group) and animals that received a dose of 15 mg/kg melatonin just after the hypoxic-ischemic event and repeated twice with an interval of 24 hours (HI+MEL group). Pups without ischemia or hypoxia were used as controls (Sham group). Seven days after surgery, brains were collected and coronal sections Nissl-stained, TUNEL-labeled, or MBP- and GFAP-immunolabeled prior to determining brain infarct area, quantify surviving neurons and evaluate oligodendroglial injury and reactive astrogliosis. The number of surviving neurons showing a well preserved architecture in HI+MEL group was similar to that observed in the Sham group. Moreover, TUNEL-positive cells only appeared in the HI group. The ratio of left-to-right hemispheric MBP immunostaining showed a significant decrease in the HI group in comparison with Sham pups, which was restored after melatonin administration. Melatonin also reduced reactive gliosis. Thus, our results suggest that treatment with melatonin after neonatal hypoxia-ischemia led to a neuroprotective effect reducing cell death, white matter demyelination and reactive astrogliosis.
Open Access
Influence of light intensity on plasma melatonin and locomotor activity rhythms in tench
(2005) Vera, L.M.; López Olmeda, J.F.; Bayarri, M.J.; Madrid, J.A.; Sánchez Vázquez, F.J.; Fisiología
Melatonin production by the pineal organ is influenced by light intensity, as has been described in most vertebrate species, in which melatonin is considered a synchronizer of circadian rhythms. In the case of tench, strict nocturnal activity rhythms have been described although the role of melatonin has not been clarified. In this study we investigated daily activity and melatonin rhythms under 12:12 light-dark (LD) conditions with two different light intensities (58.6 and 1091µW/cm2 ), and the effect of one hour broad spectrum white light pulses of different intensities (3.3, 5.3, 10.5, 1091.4 µW/cm2 ) applied at mid darkness (MD) on nocturnal circulating melatonin. The results showed that plasma melatonin in tench under LD 12:12 and high light conditions displayed a rhythmic variation, where values at MD (255.8 ± 65.9 pg/ml) were higher than at mid light (ML) (70.7 ± 31.9 pg/ml). Such a difference between MD and ML values was reduced in animals exposed to LD 12:12 and low light intensity. The application of one hour light pulses at MD lowered plasma melatonin to 111.6 ± 3.2 pg/ml (in the 3.3-10.5 µW/cm2 range) and to 61.8 ± 18.3 pg/ml (with the 1091.4 µW/cm2 light pulse) and totally suppressed nocturnal locomotor activity. These results showed that melatonin rhythms persisted in tench exposed to low light intensity although the amplitude of the rhythm is affected. In addition, it was observed that light pulses applied at MD affected plasma melatonin content and locomotor activity. Such a low threshold suggests that the melatonin system is capable of transducing light even under dim conditions, which may be used by this nocturnal fish to synchronize to weak night light signals (e.g. moonlight cycles)
Open Access
Melatonin and cancer: a polyhedral network where the source matters
(MDPI, 2021-02-01) Tomas-Loba, Antonia; Bonmatí Carrión, María de los Ángeles; Anatomía Humana y Psicobiología
Melatonin is one of the most phylogenetically conserved signals in biology. Although its original function was probably related to its antioxidant capacity, this indoleamine has been “adopted” by multicellular organisms as the “darkness signal” when secreted in a circadian manner and is acutely suppressed by light at night by the pineal gland. However, melatonin is also produced by other tissues, which constitute its extrapineal sources. Apart from its undisputed chronobiotic function, melatonin exerts antioxidant, immunomodulatory, pro-apoptotic, antiproliferative, and anti-angiogenic effects, with all these properties making it a powerful antitumor agent. Indeed, this activity has been demonstrated to be mediated by interfering with various cancer hallmarks, and different epidemiological studies have also linked light at night (melatonin suppression) with a higher incidence of different types of cancer. In 2007, the World Health Organization classified night shift work as a probable carcinogen due to circadian disruption, where melatonin plays a central role. Our aim is to review, from a global perspective, the role of melatonin both from pineal and extrapineal origin, as well as their possible interplay, as an intrinsic factor in the incidence, development, and progression of cancer. Particular emphasis will be placed not only on those mechanisms related to melatonin’s antioxidant nature but also on the recently described novel roles of melatonin in microbiota and epigenetic regulation.
Open Access
Melatonin and cannabinoids: mitochondrial-targeted molecules that may reduce inflammaging in neurodegenerative diseases
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) García, Sebastián; Martín Giménez, Virna Margarita; Mocayar Marón, Feres José; Reiter, Russel J.; Manucha, Walter
Generally, the development and progression of neurodegenerative diseases are associated with advancing age, so they are usually diagnosed in late adulthood. A primary mechanism underlying the onset of neurodegenerative diseases is neuroinflammation. Based on this background, the concept of "neuroinflammaging" has emerged. In this deregulated neuroinflammatory process, a variety of immune cells participate, especially glial cells, proinflammatory cytokines, receptors, and subcellular organelles including mitochondria, which are mainly responsible for maintaining redox balance at the cellular level. Senescence and autophagic processes also play a crucial role in the neuroinflammatory disease associated with aging. Of particular interest, melatonin, cannabinoids, and the receptors of both molecules which are closely related, exert beneficial effects on the neuro- inflammatory processes that precede the onset of neurodegenerative pathologies such as Parkinson's and Alzheimer's diseases. Some of these neuroprotective effects are fundamentally related to its anti- inflammatory and antioxidative actions at the mitochondrial level due to the strategic functions of this organelle. The aim of this review is to summarize the most recent advances in the study of neuroinflammation and neurodegeneration associated with age and to consider the use of new mitochondrial therapeutic targets related to the endocannabinoid system and the pineal gland.
Open Access
Melatonin as a mediator of the gut microbiota–host interaction: implications for health and disease
(MDPI, 2023-12-23) Rol de Lama, María de los Ángeles; Bonmatí Carrión, María de los Ángeles; Fisiología
In recent years, the role played by melatonin on the gut microbiota has gained increasingly greater attention. Additionally, the gut microbiota has been proposed as an alternative source of melatonin, suggesting that this antioxidant indoleamine could act as a sort of messenger between the gut microbiota and the host. This review analyses the available scientific literature about possible mechanisms involved in this mediating role, highlighting its antioxidant effects and influence on this interaction. In addition, we also review the available knowledge on the effects of melatonin on gut microbiota composition, as well as its ability to alleviate dysbiosis related to sleep deprivation or chronodisruptive conditions. The melatonin–gut microbiota relationship has also been discussed in terms of its role in the development of different disorders, from inflammatory or metabolic disorders to psychiatric and neurological conditions, also considering oxidative stress and the reactive oxygen species-scavenging properties of melatonin as the main factors mediating this relationship.
Open Access
Melatonin as an agent for direct pulp-capping treatment
(MDPI, 2020-02-06) Guerrero Gironés, Julia; Alcaina Lorente, Antonia; Ortiz Ruiz, Clara; Ortiz Ruiz, Eduardo; Pecci Lloret, María P.; Rodríguez Lozano, Francisco Javier; Ortiz Ruiz, Antonio José; Martínez Cáceres, Carlos Manuel; Dermatología, Estomatología, Radiología y Medicina Física
Melatonin plays an essential role in the regulation of bone growth. The actions that melatonin exerts on odontoblasts may be similar to its action on osteoblasts. This research aimed to evaluate the pulp response to melatonin used for direct pulp capping to evaluate the antioxidant effect of melatonin administered orally and its influence on dental pulp. Direct pulp capping was performed on the upper molars of Sprague Dawley rats using melatonin or Mineral Trioxide Aggregate (MTA). The study groups were: MTA; Melatonin; MTA + Melatonin administered orally; and Melatonin + Melatonin administered orally. In the latter two groups, the animals drank water dosed with melatonin ad libitum (10 mg/100 mL). After 30 days, the animals were sacrificed, and 5 ml of blood, the kidneys, and the liver were extracted in order to evaluate oxidative stress using thiobarbituric acid reactive substances testing (TBARS). Fragments of the maxilla containing the study molars were prepared for histological evaluation. The degree of pulp inflammation and pulp necrosis, the presence of reparative dentin and dentin bridging the pulp chamber, the presence and regularity of the odontoblastic layer, and the presence of pulp fibrosis were evaluated. No significant differences were found between the four study groups for any of the studied histological variables. The oral administration of melatonin did not modify the local effects of MTA or melatonin on dental pulp, or reduce basal-level oxidative stress. The effect of melatonin on pulp is similar to that of MTA and may be used as an agent for direct pulp capping.
Open Access
Melatonin decreases human adipose tissue insulin sensitivity
(Wiley, 2024-06) Zambrano, Carolina; Tena Garitaonaindia, Mireia; Salmerón, Diego; Pérez‐Sanz, Fernando; Tchio, Cynthia; Picinato, María Cecilia; Sánchez de Medina, Fermín; Luján, Juan; Scheer, Frank A. J. L.; Saxena, Richa; Martínez‐Augustin, Olga; Garaulet, Marta; Ciencias Sociosanitarias
Melatonin is a pineal hormone that modulates the circadian system and exerts soporific and phase‐shifting effects. It is also involved in many other physiological processes, such as those implicated in cardiovascular, endocrine, immune, and metabolic functions. However, the role of melatonin in glucose metabolism remains contradictory, and its action on human adipose tissue (AT) explants has not been demonstrated. We aimed to assess whether melatonin (a pharmacological dose) influences insulin sensitivity in human AT. This will help better understand melatonin administration's effect on glucose metabolism. Abdominal AT (subcutaneous and visceral) biopsies were obtained from 19 participants with severe obesity (age: 42.84 ± 12.48 years; body mass index: 43.14 ± 8.26 kg/m2 ) who underwent a laparoscopic gastric bypass. AT biopsies were exposed to four different treatments: control (C), insulin alone (I) (10 nM), melatonin alone (M) (5000 pg/mL), and insulin plus melatonin combined (I + M). All four conditions were repeated in both subcutaneous and visceral AT, and all were performed in the morning at 8 a.m. (n = 19) and the evening at 8 p.m. (in a subsample of n = 12). We used western blot analysis to determine insulin signaling (using the pAKT/ tAKT ratio). Furthermore, RNAseq analyses were performed to better understand the metabolic pathways involved in the effect of melatonin on insulin signaling. As expected, insulin treatment (I) increased the pAKT/ tAKT ratio compared with control (p < .0001). Furthermore, the addition of melatonin (I + M) resulted in a decrease in insulin signaling as compared with insulin alone (I); this effect was significant only during the evening time (not in the morning time). Further, RNAseq analyses in visceral AT during the evening condition (at 8 p.m.) showed that melatonin resulted in a prompt transcriptome response (around 1 h after melatonin addition), particularly by downregulating the insulin signaling pathway. Our results show that melatonin reduces insulin sensitivity in human AT during the evening. These results may partly explain the previous studies showing a decrease in glucose tolerance after oral melatonin administration in the evening or when eating late when endogenous melatonin is present.
Open Access
Melatonin influences pancreatic cancerogenesis
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Jaworek, Jolanta; Leja-Szpak, Anna
Pancreatic cancer has fatal prognosis because of the absence of early symptoms, late diagnosis and the resistance to radio- and chemotherapy. Melatonin, an indoleamine discovered in the pineal gland, has also been detected in the gastrointestinal system and its specific receptors have been identified in the pancreas. Some evidence indicates that melatonin could modulate the process of pancreatic oncogenesis: 1) Melatonin, as direct scavenger of radical oxygen and nitrogen species (ROS and RNS) and activator of antioxidant enzymes effectively protects the pancreatic tissue against oxidative stress and inflammatory damage. 2) In pancreatic carcinoma cell line (PANC-1) melatonin used at high doses affects the Bax/Bcl protein balance, and stimulates the expressions of caspase-9 and caspase-3, thus activating the mitochondrial pathway of apoptosis. On the contrary, low concentrations of melatonin turn on the production of anti-apoptotic heat shock proteins: HSP27, HSP70, and HSP90, which prevents the activation of caspase-3. 3) Melatonin reduces angiogenesis and decreases proliferation of endothelial cells through inhibition of vascular endothelial factor (VEGF). 4) Melatonin strengthens the immune defense of the organism via activation of peripheral effector T cells and suppression of T regulatory cells. 5) In animal studies melatonin has been found to increase the efficacy of oncostatic drugs, to reduce the side effects of chemotherapy and to decrease morbidity. These observations suggest that melatonin at high doses could be potentially taken into consideration as the supportive treatment in the therapy of pancreatic cancer, although the effect of melatonin on apoptosis requires further study. Histol Histopathol 29, 423-431 (2014)