Magnetic field effects on pineal indoleamine metabolism and possible biological consequences

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154466/1/fsb2006006004.pd

Clinical Uses of Melatonin in Pediatrics

This study analyzes the results of clinical trials of treatments with melatonin conducted in children, mostly focused on sleep disorders of different origin. Melatonin is beneficial not only in the treatment of dyssomnias, especially delayed sleep phase syndrome, but also on sleep disorders present in children with attention-deficit hyperactivity, autism spectrum disorders, and, in general, in all sleep disturbances associated with mental, neurologic, or other medical disorders. Sedative properties of melatonin have been used in diagnostic situations requiring sedation or as a premedicant in children undergoing anesthetic procedures. Epilepsy and febrile seizures are also susceptible to treatment with melatonin, alone or associated with conventional antiepileptic drugs. Melatonin has been also used to prevent the progression in some cases of adolescent idiopathic scoliosis. In newborns, and particularly those delivered preterm, melatonin has been used to reduce oxidative stress associated with sepsis, asphyxia, respiratory distress, or surgical stress. Finally, the administration of melatonin, melatonin analogues, or melatonin precursors to the infants through the breast-feeding, or by milk formula adapted for day and night, improves their nocturnal sleep. Side effects of melatonin treatments in children have not been reported. Although the above-described results are promising, specific studies to resolve the problem of dosage, formulations, and length of treatment are necessary

Wpływ melatoniny, N-acetyloserotoniny i 6-hydroksymelatoniny na ultrastrukturę pinealocytów chomika syryjskiego (Mesocricetus auratus)

Objectives: The aim of this study was to examine the effects of melatonin as well as of its precursor (N-acetylserotonin) and metabolite (6-hydroxymelatonin) on the ultrastructure of the pinealocytes of the Syrian hamster. Material and methods: The pineal glands of 2-month-old male Syrian hamsters were examined. The animals were divided into the following groups of four animals each: group 1 - melatonin treatment; group 2 - N-acetylserotonin treatment; group 3 - 6-hydroxymelatonin treatment (all substances given subcutaneously at doses of 25 μg per animal between 16.00 and 17.00 h daily for seven weeks). Group 4 was given solvent treatment only and served as controls. The animals were killed by decapitation between 09:00 and 10.00 h. Routine electron microscopical techniques were used to obtain quantitative data on pinealocyte ultrastructure. Results: Melatonin administration did not influence the size of the hamster pinealocytes, whereas administration of N-acetylserotonin and 6-hydroxymelatonin caused a significant reduction in cell size in comparison to the melatonintreated and control groups. There were changes in the relative volumes of the mitochondria, Golgi apparatus and lysosomes in the pinealocytes of the studied groups, while the volumes of granular endoplasmic reticulum and lipid droplets were unchanged. The dense-core vesicles were more numerous in the pinealocytes of the melatonin and 6-hydroxymelatonin-treated groups in comparison to those of animals treated with N-acetylserotonin or the controls. Conclusions: The changes observed in the ultrastructure of hamster pinealocytes indicate that administration of melatonin as well as of its precursor or metabolite influences the morphology of these cells and also, perhaps, their secretory activity.Wstęp: Celem niniejszego badania była ocena wpływu melatoniny, a także jej prekursora (N-acetyloserotoniny) i metabolitu (6-hydroksymelatoniny) na ultrastrukturę pinealocytów chomika syryjskiego. Materiał i metody: Badano szyszynki 2-miesięcznych samców chomików syryjskich. Zwierzęta podzielono na następujące grupy, liczące po 4 zwierzęta każda: grupa 1. - otrzymująca melatoninę; grupa 2. - otrzymująca N-acetyloserotoninę; grupa 3. - otrzymująca 6-hydroksymelatoninę (wszystkie substancje podawano podskórnie przez 7 tygodni, w dawce 25 μg/zwierzę, między godz. 16. a 17.). Zwierzęta z grupy 4. otrzymujące jedynie rozpuszczalnik stanowiły grupę kontrolną. Zwierzęta zabijano przez dekapitację między godziną 9. a 10. W celu uzyskania ilościowych danych dotyczących ultrastruktury pinealocytów stosowano rutynowe techniki mikroskopowo-elektronowe. Wyniki: Podawanie melatoniny nie wpłynęło na wielkość pinealocytów, podczas gdy wstrzyknięcia N-acetyloserotoniny i 6-hydroksymelatoniny spowodowały znaczne zmniejszenie rozmiarów tych komórek w porównaniu z grupą kontrolną i zwierzętami otrzymującymi melatoninę. Stwierdzono istotne zmiany we względnych objętościach mitochondriów, aparatu Golgiego i lizosomów między badanymi grupami, natomiast objętości ziarnistej siateczki śródplazmatycznej i kropli lipidów nie wykazywały różnic między badanymi grupami. Pęcherzyki ziarniste były liczniejsze w pinealocytach chomików otrzymujących melatoninę lub 6-hydroksymelatoninę niż u zwierząt kontrolnych lub otrzymujących N-acetyloserotoninę. Wnioski: Obserwowane zmiany w ultrastrukturze pinealocytów chomika syryjskiego świadczą, że podawanie zarówno melatoniny, jak i jej prekursora lub metabolitu wpływa na morfologię tych komórek i prawdopodobnie także na ich aktywność wydzielniczą

Neurotoxins: Free Radical Mechanisms and Melatonin Protection

Toxins that pass through the blood-brain barrier put neurons and glia in peril. The damage inflicted is usually a consequence of the ability of these toxic agents to induce free radical generation within cells but especially at the level of the mitochondria. The elevated production of oxygen and nitrogen-based radicals and related non-radical products leads to the oxidation of essential macromolecules including lipids, proteins and DNA. The resultant damage is referred to as oxidative and nitrosative stress and, when the molecular destruction is sufficiently severe, it causes apoptosis or necrosis of neurons and glia. Loss of brain cells compromises the functions of the central nervous system expressed as motor, sensory and cognitive deficits and psychological alterations. In this survey we summarize the publications related to the following neurotoxins and the protective actions of melatonin: aminolevulinic acid, cyanide, domoic acid, kainic acid, metals, methamphetamine, polychlorinated biphenyls, rotenone, toluene and 6-hydroxydopamine. Given the potent direct free radical scavenging activities of melatonin and its metabolites, their ability to indirectly stimulate antioxidative enzymes and their efficacy in reducing electron leakage from mitochondria, it would be expected that these molecules would protect the brain from oxidative and nitrosative molecular mutilation. The studies summarized in this review indicate that this is indeed the case, an action that is obviously assisted by the fact that melatonin readily crosses the blood brain barrier

A comparison of melatonin and α-lipoic acid in the induction of antioxidant defences in L6 rat skeletal muscle cells.

Aging is characterized by a progressive deterioration in physiological functions and metabolic processes. The loss of cells during aging in vital tissues and organs is related to several factors including oxidative stress and inflammation. Skeletal muscle degeneration is common in elderly people; in fact, this tissue is particularly vulnerable to oxidative stress since it requires large amounts of oxygen, and thus, oxidative damage is abundant and accumulates with increasing age. Melatonin (N-acetyl-5-methoxytryptamine) is a highly efficient scavenger of reactive oxygen species and it also exhibits beneficial anti-inflammatory and anti-aging effects. This study investigated the susceptibility of rat L6 skeletal muscle cells to an induced oxidative stress following their exposure to hydrogen peroxide (50 μM) and evaluating the potential protective effects of pre-treatment with melatonin (10 nM) compared to the known beneficial effect of alpha-lipoic acid (300 μM). Hydrogen peroxide-induced obvious oxidative stress; it increased the expression of tumour necrosis factor-alpha and in turn promoted nuclear factor kappa-B and overrode the endogenous defence mechanisms. Conversely, pre-treatment of the hydrogen peroxide-exposed cells to melatonin or alpha-lipoic acid increased endogenous antioxidant enzymes, including superoxide dismutase-2 and heme oxygenase-1; moreover, they ameliorated significantly oxidative stress damage and partially reduced alterations in the muscle cells, which are typical of aging. In conclusion, melatonin was equally effective as alpha-lipoic acid; it exhibited marked antioxidant and anti-aging effects at the level of skeletal muscle in vitro even when it was given in a much lower dose than alpha-lipoic acid

Assessment of the Potential Role of Tryptophan as the Precursor of Serotonin and Melatonin for the Aged Sleep-wake Cycle and Immune Function: Streptopelia Risoria as a Model

In the present review we summarize the relationship between the amino acid, tryptophan, the neurotransmitter, serotonin, and the indole, melatonin, with the rhythms of sleep/wake and the immune response along with the possible connections between the alterations in these rhythms due to aging and the so-called “serotonin and melatonin deficiency state.” The decrease associated with aging of the brain and circulating levels of serotonin and melatonin seemingly contributes to the alterations of both the sleep/wake cycle and the immune response that typically accompany old age. The supplemental administration of tryptophan, e.g. the inclusion of tryptophan-enriched food in the diet, might help to remediate these age-related alterations due to its capacity of raise the serotonin and melatonin levels in the brain and blood. Herein, we also summarize a set of studies related to the potential role that tryptophan, and its derived product melatonin, may play in the restoration of the aged circadian rhythms of sleep/wake and immune response, taking the ringdove (Streptopelia risoria) as a suitable model

Tunneling nanotubes and mesenchymal stem cells: new insights into the role of melatonin in neuronal recovery

none5sìEfficient cell-to-cell communication is essential for tissue development, homeostasis, and the maintenance of cellular functions after injury. Tunneling nanotubes (TNTs) have emerged as a new important method of cell-to-cell communication. TNTs are primarily established between stressed and unstressed cells and can transport a variety of cellular components. Mitochondria are important trafficked entities through TNTs. Transcellular mitochondria transfer permits the incorporation of healthy mitochondria into the endogenous network of recipient cells, changing the bioenergetic profile and other functional properties of the recipient and may allow the recipient cells to recuperate from apoptotic processes and return to a normal operating state. Mesenchymal cells (MSCs) can form TNTs and transfer mitochondria and other constituents to target cells. This occurs under both physiological and pathological conditions, leading to changes in cellular energy metabolism and functions. This review summarizes the newly-described capacity of melatonin to improve mitochondrial fusion/fission dynamics and promote TNT formation. This new evidence suggests that melatonin’s protective effects could be attributed to its ability to prevent mitochondrial damage in injured cells, reduce senescence, and promote anastasis, a natural cell recovery phenomenon that rescues cells from the brink of death. The modulation of these new routes of intercellular communication by melatonin could play a key role in increasing the therapeutic potential of MSCs.openLuchetti, Francesca; Carloni, Silvia; Nasoni, Maria G.; Reiter, Russel J.; Balduini, WalterLuchetti, Francesca; Carloni, Silvia; Nasoni, Maria G.; Reiter, Russel J.; Balduini, Walte

Evidence of melatonin ameliorative effects on the blood-testis barrier and sperm quality alterations induced by cadmium in the rat testis.

Herein, we further document the protective action of melatonin (MLT) in mitigating cadmium (Cd)-induced toxicity on male adult rat testis. Cd treatment provoked testicular injury, that was documented by histological and biomolecular alterations, i.e., decrease of serum and testicular testosterone concentration and modified sperm parameters. Mainly, both the cytoarchitecture of the blood-testis barrier (BTB) and germ cell morphology were perturbed, as highlighted by impairment in structural (OCN, VANGL, Cx43) and regulative (Src and FAK) protein levels and/or activation. The study focused on the involvement of the autophagy pathway, that was enhanced especially in the Sertoli cells, probably in response to the disorganization of the BTB. Results obtained with the MLT co-treatment demonstrated that its administration decreased the level of oxidative damage caused by Cd, with reversal of all the observed changes. Moreover, the beneficial effects of MLT alone were evidenced by an increase of sperm quality, in term of motility and DNA integrity. The combined results, obtained in rat, strongly encourage to consider a role for MLT in improving also human testicular health, not only in men exposed to Cd, but also in those having fertility disorders, to ameliorate sperm quality and, consequently, reproductive success

Altered Expression of DAAM1 and PREP Induced by Cadmium Toxicity is Counteracted by Melatonin in the Rat Testis.

Cadmium (Cd) is one of the most toxic pollutants for health due to its accumulation in several tissues including testis. This report confirms that Cd increased oxidative stress and apoptosis of germ and somatic cells, provoked testicular injury, as documented by biomolecular and histo-logical alterations, i.e., CAT and SOD activity, the protein level of steroidogenic enzymes (StAR and 3β-HSD), and morphometric parameters. Additionally, it further documents the melatonin (MLT) coadministration effects in mitigating Cd-induced toxicity on adult rat testis, as demon-strated by the reduction of oxidative stress and apoptosis, with reversal of the observed histolog-ical changes; moreover, a role of MLT in partially restoring steroidogenic enzymes expression was evidenced. Importantly, the cytoarchitecture of testicular cells was perturbed by Cd exposure, as highlighted by impairment of the expression and localization of two cytoskeleton-associated proteins DAAM1 and PREP, involved in the germ cells differentiation into spermatozoa, altering the normal spermatogenesis. Here, for the first time, we found that the co-treatment with MLT at-tenuated the Cd-induced toxicity on the testicular DAAM1 and PREP expression. The combined findings provide additional clues about a protective effect of MLT against Cd-induced testicular toxicity, acting on DAAM1 and PREP expression, encouraging further studies to prove its effec-tiveness in human health