bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between melatonin and estradiol on morphological and morphometric features of MCF‐7 human breast cancer cells
Authors: Crespo O. , Fernandez‐Viadero C. , Verduga R. , Ovejero V. , Cos S. 
Published: February 2007

Crespo D, Fernández‐Viadero R, Verduga R, Ovejero V, Cos S. Interaction'between melatonin and estradiol on morphological and morphometric features of MCF‐7 human breast cancer cells. J. Pineal Res. 1994:16:215–222.AbstractMelatonin has been shown to have a direct inhibitory effect on the proliferation of estrogen‐responsive MCF‐7 human breast cancer cells, involving an interaction with estradiol. The anti‐proliferative effect of melatonin is reversed by the addition of estradiol to the culture. In the present study, we examined whether inhibition by megaton and subsequent estrogen rescue of MCF‐7 cells are correlated with morphological and morph metric changes in these cells. After 4 days of exposure to melatonin, MCF‐7 cells showed significantly smaller cell and nuclear sizes than other groups. These morphometric results were closely related to the ultra structural features observed in these cells. While control and estradiol‐treated cells showed increased tumor characteristics, melatonin‐treated cells presented greater differentiation, in keeping with their epithelial origin (presence of cytokeratin filament bundles, conspicuous rough endoplasmic reticulum, and Golgi cisternae together with the presence of prominent nucleoli at the nuclear level). Additionally, some melatonin‐treated cells displayed degenerative features (mitochondrial swelling with disruption of cristae, cytoplasmic vacuolation, nuclear chromatin disgregation and cell lysis). The addition of estradiol to cells previously incubated with melatonin reversed the changes induced by the latter and these cells showed the same ultrastructural features as the control cells. Our results support the notion that melatonin exerts its antitumor effect through a cell‐cycle‐specific mechanism by delaying the entry of MCF‐7 cells into mitosis. This allows the tumor cells to achieve greater differentiation. The fact that the morph metric and morphological effects induced by megaton are counteracted by estrogens suggests a cell‐cycle acceleration induced by estradiol.
Immunohistochemical studies on the coexistence of catecholamine‐synthesizing enzymes and neuropeptide Y in nerve fibers of the porcine pineal gland
Authors: Kaleczyc Jerzy , Przybylska Barbara , Majewski Mariusz , Lewczuk Bogdan 
Published: February 2007

Kaleczyc J, Przybylska B, Majewski M, Lewczuk B. Immunohistochemical studies on the coexistence of catecholamine‐synthesizing enzymes and neuropeptide Y in nerve fibers of the porcine pineal gland. J. Pineal Res. 1994: 17: 20–24.AbstractThe distribution of nerve fibers immunoreactive (IR) to catecholamine‐synthesizing enzymes, tyrosine hydroxylase (TH), dopamine‐β‐hydroxylase (DβH), and phenylefhanolamine‐N‐methyltransferase (PNMT) as well as neuropeptide Y (NPY), in the pineal gland of adult sows was investigated by the use of double‐labeling immunohistochemistry. The porcine pineal gland was found to be supplied by TH‐IR nerve fibers, the vast majority of which were also DBH‐positive. TH‐ and TH/DβH‐IR nerves were located mostly in the capsula and connective septa of the pineal gland, and their fine varicose branches terminated in the adherent parenchyma. NPY‐IR fibers formed a loose network overlapping that was observed in the case of TH‐and DβH‐IR fibers. Most of NPY‐IR fibers were also positive for TH. The density of the fiber networks depended on the region of the gland. No PNMT‐IR structures were observed.
Inhibitory effect of melatonin on cataract formation in newborn rats: Evidence for an antioxidative role for melatonin
Authors: Abe Mitsushi , Reiter Russel J. , Orhii Paul B. , Hara Masayuki , Poeggeler Burkhard 
Published: February 2007

Abe M, Reiter RJ, Orhii PB, Hara M, Poeggeler B. Inhibitory effect of melatonin on cataract formation in newborn rats: Evidence for an antioxidative role for melatonin. J. Pineal Res. 1994; 17: 94–100. ©Munksgaard 1994AbstractWe evaluated the inhibitory effect of melatonin, a recently discovered scavenger of free radicals, on cataract formation in the newborn rat. The glutathione synthesis inhibitor, buthionine sulfoximine (BSO) (3 mmol/kg), was intraperitoneally injected into newborn rats for 3 consecutive days starting on day 2 after birth. These glutathione depleted rats develop cataracts. Melatonin (4 mg/kg) was injected intraperitoneally into half of the rats once a day beginning at day 2 after birth; the other half of the animals received solvent daily. The incidence of cataract was observed on day 16, after the eyes of the newborn animals had opened. Both reduced glutathione (GSH) and oxidized glutathione (GSSG) levels were measured. Cataracts were observed in all animals (18/18) treated with BSO plus solvent. The incidence of the cataract in the animals cotreated with melatonin was only 6. 2% (1/15). Total lenticular glutathione (GSH + GSSG) levels in BSO only treated rats were reduced by 97%. The total glutathione in the lens of the BSO plus melatonin group was significantly higher (by 3%) than that of the BSO only group. The percentage of the total glutathione as GSSG for the BSO plus solvent group was higher than the control value. Cotreatment of BSO injected rats with melatonin (4 mg/kg/day) clearly reduced cataract formation proving that it is directly or indirectly protective against oxidative stress which accompanies glutathione deficiency. The inhibitory effects of melatonin on cataract formation in this study could be due to melatonin's free radical scavenging activity or due to its stimulatory effect on glutathione production.
Inhibitory effect of melatonin on production of IFNγ or TNFα in peripheral blood mononuclear cells of some blood donors
Authors: Di Stefano Anna , Paulesu Luana 
Published: February 2007

Di Stefano A, Paulesu L. Inhibitory effect of melatonin on production of IFNγ or TNFα in peripheral blood mononuclear cells of some blood donors. J. Pineal Res. 1994;17:164–169.AbstractMelatonin, the main pineal hormone, has been shown to influence many biological functions, including the immune response and cancer growth. The purpose of this study was to examine the effect of melatonin on the production of interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) by peripheral blood mononuclear cells (PBMC) in culture. Melatonin at physiological concentrations fails to induce production of IFN or TNF by PBMC in culture but causes a dose‐related inhibition of production of both cytokines if the PBMC are stimulated with phytohaemagglutinin. This inhibitory effect occurs in only 22% of cases (melatonin‐sensitive) but disappears when the cells are stored at 4°C for 4 days. The effect of melatonin appears not to be mediated by opiates nor to be correlated with the age, sex, or blood group of donors, but seems to be influenced by the seasonal time of blood collection. These results provide further evidence for an interaction between melatonin and the immune system and suggest that the effect of melatonin on production of IFN and TNF may be mediated by various factors not yet fully understood.
Response of collared lemmings to melatonin: II. Infusions and photoperiod
Authors: Gower Barbara A. , Hadjipanayis Constantinos , Nagy Tim R. , Stetson Milton H. 
Published: February 2007

Gower BA, Hadjipanayis C, Nagy TR, Stetson MH. Response of collared lemmings to melatonin: II. Infusions and photoperiod. J. Pineal Res. 1994:17:185–194.AbstractCollared lemmings (Dicrostonyx groenlandicus) show much phenotypic plasticity when exposed to photoperiods of varying length. In addition to “long day” and “short day” morphologies, apparent when animals are exposed to 22L:2D and 8L:16D, respectively, animals with intermediate features appear when collared lemmings are placed on day lengths ranging from 18L:6D to 14L:10D. Body mass, body composition, pelage color and length, the presence and size of a bifid claw, and reproductive condition are all influenced by ambient day length. We tested the hypothesis that variations in the melatonin signal mediate the physiological and morphological responses observed in collared lemmings housed in various photoperiods. One group of collared lemmings was fitted with a subcutaneous cannula at weaning and infused for 8 weeks with 2, 6, or 14 hr melatonin or 14 hr vehicle daily while housed in constant light (LL). Additional groups were transferred to LL, 20L:4D, 16L:8D, or 8L:16D (all uninfused). The response of the animals to both melatonin infusion and photoperiod was graded; the degree to which the “winter” morphology developed was proportional to the length of both the melatonin infusion and the scotophase. Both the 14 hr infusion and the 8L:16D photoperiod promoted development of the characteristic “winter” traits: large body size, white pelage, bifid claw, small uterus, and low serum prolactin (PRL). Conversely, treatment with the 2 hr infusion or exposure to the long photoperiods (LL, 20L:4D) resulted in a “summer‐like” morphology. Infusion of 6 hr melatonin per day or exposure to 16L:8D produced animals with an intermediate physiology. Overall, the results support the hypothesis that variations of the endogenous melatonin rhythm mediate the effect of photoperiod length on seasonal physiological and morphological changes in collared lemmings.
The influence of cervical sympathetic neurons on parathyroid hormone and calcitonin release in the rat: Independence of pineal mediation
Authors: Stern Javier E. , Esquifino Ana I. , Bonacho Manuel Garcia , Cardinali Daniel P 
Published: February 2007

Stern JE, Esquifino AI, Bonacho MG, Cardinali DP. The influence of cervical sympathetic neurons on parathyroid hormone and calcitonin release in the rat: Independence of pineal mediation. J. Pineal Res. 1997; 22:9–15. © Munksgaard, CopenhagenAbstractThe objective of this study was to evaluate the involvement of the pineal gland in modulation of parathyroid hormone (PTH) and calcitonin release found in rats after changes in activity of cervical sympathetic nerves. The response of serum PTH to a hypocalcemia produced by EDTA injection, and of serum calcitonin to a hypercalcemia produced by administering calcium chloride, were studied in rats at the time of the wallerian degeneration of regional sympathetic nerves (i.e., 16 hr after superior cervical ganglionectomy, SCGx). Rats received a pinealectomy or its sham‐operation 4 days before SCGx. During wallerian degeneration of nerves after SCGx, a higher hypocalcemia and a lower PTH response were found as compared to sham‐SCGx rats, regardless of whether the pineal gland was present or not. When the response of calcitonin to a bolus injection of calcium chloride was assessed, rats subjected to SCGx 16 hr earlier showed a depressed calcitonin release, which was also unaffected after pinealectomy. To a similar extent in pinealectomized and sham‐pinealectomized rats, a mild stress given by the subcutaneous injection of turpentine oil brought about a greater hypocalcemia after EDTA, concomitantly with a higher PTH secretory response. In turpentine oil‐injected rats, the rise of serum calcitonin was significantly greater than that of vehicle‐treated rats, regardless of pineal presence. The results further indicate that cervical autonomic nerves constitute a pathway through which the brain modulates calcium homeostasis and do not support the participation of the pineal gland in short term changes of PTH or calcitonin release.
Potentially beneficial cardiovascular effects of melatonin administration in women
Authors: Cagnacci Angelo , Arangino Serenella , Angiolucci Marco , Maschio Elisabetta , Longu Giorgio , Metis Gian Benedetto 
Published: February 2007

Cagnacci A, Arangino S, Angiolucci M, Maschio E, Longu G, Melis GB. Potentially beneficial cardiovascular effects of melatonin administration women. J. Pineal Res. 1997; 22:16–19. Munksgaard, CopenhagenAbstractThe cardiovascular effects induced by the daytime administration of melatonin (1 mg) were compared to those of placebo in 12 young women. In order to eliminate cardiovascular effects due to fluctuating endogenous sex steroids, all women were taking a fixed dose of monophasic contraceptive pill. In comparison to placebo, the administration of melatonin reduced, within 90 min, the pulsatility index of the internal carotid artery, evaluated by color Doppler ultrasound (P<0.01), as well as both systolic and diastolic blood pressure evaluated in supine position (P<0.01). Supine catecholamine levels were not significantly modified, but norepinephrine levels evaluated after 5 min of standing position were significantly reduced (P<0.02). These data suggest that in women the administration of 1 mg of melatonin may exert beneficial effects on blood vessels.
Histamine in the chick pineal gland: Origin, metabolism, and effects on the pineal function
Authors: Nowak Jerzy Z. , Zawilska Jolanta B. , Woldan‐Tambor Agata , Sçk Barbara , Voisin Pierre , Lintunen Minnamaija , Panula Pertti 
Published: February 2007

Nowak JZ, Zawilska JB, Woldan‐Tambor A, Sçk B, Voisin P, Lintunen M, Panula P. Histamine in the chick pineal gland: Origin, metabolism, and effects on the pineal function. J Pineal Res. 1997; 22:26–32. © Munksgaard, CopenhagenAbstractThe chick pineal gland contains histamine andtele‐methylhistamine. The levels of both substances are elevated after treatment of chicks with the amino acid precursor of histamine, L‐histidine (1 g/kg, ip). In control and L‐histidine‐loaded animals the pineal levels of histamine andtele‐methylhistamine are higher in light‐exposed than in dark‐adapted animals (measured at the end of the light phase and in the middle of the dark phase of 12 hr light, 12 hr dark illumination cycle, respectively). The chick pineal gland contains histamine‐immunofluorescent cells displaying mast cell morphology; they are seen in the vicinity of the capsule and in the parenchyma. Enzymatic studies showed the presence of the activity of histamine synthesizing and inactivating enzyme, i.e., L‐histidine decarboxylase (HDC) and histamine‐methyltransferase (HMT). The detected enzyme activities were sensitive to specific inhibitors of HDC (α‐fluoromethylhistidine and α‐hydrazinohistidine) and HMT (quinacrine and metoprine); inhibitors of aromatic amino acid decarboxylase α‐methyl‐DOPA and NSD‐1015 were inactive on HDC. Exogenous histamine added to organ‐cultured chick pineals strongly stimulated endogenous cyclic AMP accumulation and moderately increased melatonin secretion. The data, considered collectively, suggest that in avians histamine, probably originating from the pineal mast cell compartment, may function as a regulator of pineal gland activity.
Pharmacokinetics and oral bioavailability of exogenous melatonin in preclinical animal models and clinical implications
Authors: Yeleswaram Krishnaswamy , McLaughlin Lee G. , Knipe Jay O. , Schabdach David 
Published: February 2007

Yeleswaram K, McLaughlin LG, Knipe JO, Schabdach D. Pharmacokinetics and oral bioavailability of exogenous melatonin in preclinical animal models and clinical implications. J. Pineal Res. 1997; 22:45–51. © Munksgaard, CopenhagenAbstractA review of the literature indicates that the absolute oral bioavailability of exogenous melatonin in humans or in preclinical animal models has not been adequately characterized; hence, this study was undertaken. Pharmacokinetics of melatonin was studied in rats, dogs, and monkeys following intravenous and oral administrations, and the absolute oral bioavailability of melatonin was calculated from the area under the plasma concentration‐time curve. The apparent elimination half‐life of melatonin following an intravenous dose of 3 mg/kg (5 mg/kg in rats) was 19.8, 18.6, and 34.2 minutes, respectively, in rats, dogs, and monkeys. The dose normalized oral bioavailability of melatonin following a 10 mg/kg oral dose was 53.5% in rats, while it was in excess of 100% in dogs and monkeys. Further, bioavailability of melatonin following a 10 mg/kg intraperitoneal administration in rats was 74.0%, suggesting the lack of substantial first‐pass hepatic extraction of melatonin in rats. However, the oral bioavailability of melatonin in dogs decreased to 16.9% following a 1 mg/kg oral dose, indicating dose‐dependent bioavailability in dogs. In vitro permeability studies with CACO‐2 cells suggest that melatonin is likely to be well absorbed in humans. In vitro metabolism studies with fresh liver slices from rats as well as human donors were conducted to compare the initial rates of metabolism of melatonin between the two species and the results suggest that the intrinsic clearance of melatonin in humans may be lower than that in rats.
Protective effect of melatonin in carrageenan‐induced models of local inflammation: Relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity
Authors: Cuzzocrea Salvatore , Zingarelli Basilia , Gilad Eli , Hake Paul , Salzman Andrew L. , Szabó Csaba 
Published: February 2007

Cuzzocrea S, Zingarelli B, Gilad E, Hake P, Salzman AL, Szabó C. Protective effect of melatonin in carrageenan‐induced models of local inflammation: Relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity. J. Pineal Res. 1997; 23:106–116. © Munksgaard, CopenhagenAbstractIn vitro studies have demonstrated that melatonin is a scavenger of oxyradicals and peroxynitrite and an inhibitor of nitric oxide (NO) production. In the present study, we evaluated the effect of melatonin treatment in two models of acute inflammation (carrageenan‐induced paw edema and pleurisy), where oxyradicals, NO, and peroxynitrite play a crucial role in the inflammatory process. Our data show that melatonin (given at 62.5 and 125 μg/paw in the paw edema model or 25 and 50 mg/ kg in the pleurisy model) inhibits the inflammatory response (paw swelling, pleural exudate formation, mononuclear cell infiltration, and histological injury) in dose‐dependent manner in both models. Furthermore, our data suggest that melatonin exerts an inhibitory effect on the expression of the inducible isoform of NO synthase. Melatonin also prevented the formation of nitrotyrosine, an indicator of peroxynitrite, in both models of inflammation. Taken together, the present results demonstrate that melatonin exerts potent antiinflammatory effects. Part of these antiinflammatory effects may be related to an inhibition of the expression of the inducible NO synthase, while another part may be related to oxyradical and peroxynitrite scavenging.
Synchronization by low‐amplitude light‐dark cycles of 24‐hour pineal and plasma melatonin rhythms of hatchling European starlings (Sturnus vulgaris)
Authors: Gwinner E. , Zeman M. , Klaassen M. 
Published: February 2007

Gwinner E, Zeman M, Klaassen M. Synchronization by low‐amplitude light‐dark cycles of 24‐hour pineal and plasma melatonin rhythms of hatchling European starlings (Sturnus vulgaris). J. Pineal Res. 1997; 23:176–181. © Munksgaard, CopenhagenAbstractIn young European starlings, as in other avian species, high‐amplitude 24‐hr rhythms in plasma and pineal melatonin are already present around the time of hatching. In chickens this rhythmicity results at least partly from the light sensitivity of the melatonin‐producing and ‐secreting system. In contrast to the chicken, the starling is a hole‐nesting bird, and it seemed questionable whether the low light intensities in the nest are sufficient to synchronize perinatal melatonin rhythms. We therefore exposed starling eggs to light cycles roughly simulating those measured in nest‐boxes, i.e., an 11‐hr phase of complete darkness and a 13‐hr phase consisting of 15 min of dim light (10 lux) alternating with 30 min of darkness. For one group the photophase lasted from 0600 to 1900 hr; for the other group the photophase lasted from 1800 to 0700 hr. In approximately 10‐hr‐old hatchlings of both groups, plasma and pineal melatonin concentrations were high during the dark phase and low during the light phase. We conclude that perinatal low‐amplitude light intensity changes of the kind experienced by hatching starlings in the field are sufficient for synchronizing the melatonin‐producing and ‐secreting system in the pineal and possibly other organs.
In vivo protection by melatonin against δ‐aminolevulinic acid‐induced oxidative damage and its antioxidant effect on the activity of haem enzymes
Authors: Princ Fernando G. , Maxit Andrea G. , Cardalda Carina , Batlle Alcira , Ana Juknat Adela 
Published: February 2007

Princ FG, Maxit AG, Cardalda C, Batlle A, Juknat AA. In vivo protection by melatonin against δ‐aminolevulinic acid‐induced oxidative damage and its antioxidant effect on the activity of haem enzymes. J. Pineal Res. 1998; 24:1–8. © Munksgaard, CopenhagenAbstractAccumulation of 8‐aminolevulinic acid (ALA), as it occurs in acute intermittent porphyria, is a potential endogenous source of reactive oxygen species (ROS) which can then produce oxidative damage to cell structures and macromolecules. This in vivo study investigated whether melatonin could prevent the deleterious effects of ALA. Rats were injected i.p. for 2 weeks with ALA (40 mg/kg on alternate days) and/or with melatonin (50 μg/kg or 500 μg/kg daily). Administration of pharmacological doses of melatonin reduced and/or prevented ALA‐induced lipid peroxidation (LPO) in both cerebral cortex and cerebellum, providing further evidence of melatonin's action as a ROS scavenger. Administration of pharmacological concentrations of melatonin to ALA‐injected rats showed the protective properties of melatonin on the activities of both porphobilinogen‐deaminase and δ‐aminolevulinate dehydratase (ALA‐D) in the cerebral cortex; the effect on ALA‐D activity was unexpectedly high (at least 6‐fold), indicating that, besides acting as a scavenger of hydroxyl radicals, melatonin may exert its protection on ALA‐D through other mechanisms, such as increasing mRNA levels of antioxidant enzymes or/ and inducing glutathione peroxidase activity. The possibility that changes in the expression of antioxidant enzymes could affect the expression of other proteins, even those not related to the cellular ROS homeostasis, should also not be discarded. The potential use of melatonin as an antioxidant and for its reactivating properties in the treatment of acute porphyrias is considered.