Abstract：
:Melatonin is a highly effective treatment in different animal models of excitotoxicity or ischemia/reperfusion injury. Due to a lack of patentability, commercial sponsors are not interested in funding clinical evaluations of melatonin. Investigators may initiate small-scale clinical evaluation, and intravenous (i.v.) administration is appropriate in acute stroke patients. Institutional Review Boards may require proper preclinical evaluation of the preparation. In this pharmacokinetic and safety study, melatonin in propylene glycol was evaluated in adult male Sprague-Dawley rats. Following a single i.v. injection at 5 or 15 mg/kg, plasma concentrations of melatonin increased to 39 and 199 million pg/mL at 2 min and 128,000 and 772,000 pg/mL at 120 min. Within 60 min of injection, the blood pressure, heart rate and body temperature remained unaffected. Melatonin at 5 mg/kg did not influence the complete blood counts at 60 min, but melatonin at 15 mg/kg had some effects on the differential white cell and platelet counts. Melatonin at 5 or 15 mg/kg slightly elevated some liver enzymes at 60 min of injection, and melatonin at higher dose also elevated plasma creatinine and lactate dehydrogenase levels. At 24 hr after completion of six daily injections of melatonin, there was a 5.5% reduction in body weight. Gross postmortem examination and histological examination of the brain, kidney, liver and spleen did not reveal any evidence of toxicity. In conclusion, melatonin in propylene glycol markedly elevates plasma levels of melatonin with no serious toxicity. This preparation should be further evaluated in human patients.
journal_name
J Pineal Resjournal_title
Journal of pineal researchauthors
Cheung RT,Tipoe GL,Tam S,Ma ES,Zou LY,Chan PSdoi
10.1111/j.1600-079X.2006.00372.xsubject
Has Abstractpub_date
2006-11-01 00:00:00pages
337-43issue
4eissn
0742-3098issn
1600-079Xpii
JPI372journal_volume
41pub_type
杂志文章abstract：:The objective of this study was to apply the radioimmunoassay for 6-sulphatoxymelatonin (aMT6s) to rat urine, and use it to study the source of aMT6s. The radioimmunoassay was found to have acceptable within- and between-assay variation, excellent specificity, and good parallelism between the standard and unknown. Bec...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1991.tb00831.x
更新日期：1991-04-01 00:00:00
abstract：:Four weeks of administration of melatonin mixed in the diet (5 mg/kg of food) significantly reduced the incidence of gastric ulcers in young pigs. In control and melatonin supplemented animals, significantly higher levels of melatonin were found in the stomach tissues as compared to jejunum, ileum, or colon. Pigs with...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1998.tb00367.x
更新日期：1998-01-01 00:00:00
abstract：:Our objective was to suppress the daily surge of melatonin in serum of prepubertal dairy heifers by manipulating intensity of light (Experiment 1) and duration of exposure to light (Experiment 2). Heifers in Experiment 1 were exposed to either 12 hr of darkness (000 lux, control), or 400, 800, or 1,200 lux of light du...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1992.tb00046.x
更新日期：1992-05-01 00:00:00
abstract：:The circadian clock plays a vital role in physiology and behavior such as the sleep-wake cycle and blood pressure and hormone levels. Immune responses also display circadian rhythmicity and particularly pineal melatonin contributes to immunological processes. Little attention, however, is given to mechanisms underlyin...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12230
更新日期：2015-05-01 00:00:00
abstract：:Melatonin displays antioxidant and free radical scavenger properties. Due to its ability with which it enters cells, these protective effects are manifested in all subcellular compartments. Recent studies suggest a role for melatonin in mitochondrial metabolism. To study the effects of melatonin on this organelle we u...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1034/j.1600-079x.2000.280407.x
更新日期：2000-05-01 00:00:00
abstract：:The purpose of this study was to determine whether melatonin treatment would mitigate retinal ganglion cell (RGC) death in the developing retina following a hypoxic insult. Lipid peroxidation (LPO), glutathione (GSH), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) concentrations, expression of vascular end...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12016
更新日期：2013-03-01 00:00:00
abstract：:A 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 admin...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1997.tb00302.x
更新日期：1997-01-01 00:00:00
abstract：:In previous studies, we have shown that mitochondrial respiratory chain (MRC) activity is decreased in patients with nonalcoholic steatohepatitis and in ob/ob mice and that peroxynitrite plays a pathogenic role. The present study examined whether melatonin, a peroxynitrite scavenger, prevents: (i) the in vitro effects...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2011.00868.x
更新日期：2011-08-01 00:00:00
abstract：:Grapes are an important economic crop and are widely cultivated around the world. Most grapes are grown in arid or semi-arid regions, and droughts take a heavy toll in grape and wine production areas. Developing effective drought-resistant cultivation measures is a priority for viticulture. Melatonin, an indoleamine, ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12159
更新日期：2014-09-01 00:00:00
abstract：:Exposure of rats to light during darkness or blockade of the pineal beta-adrenoceptor in stimulated pineal glands results in a rapid fall in pineal N-acetyltransferase (NAT) activity. Maintenance of a high level of NAT activity requires continuous stimulation of the pineal beta-adrenoceptors. It is not known what fact...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1992.tb00026.x
更新日期：1992-03-01 00:00:00
abstract：:Liver fibrosis is scar tissue resulting from an uncontrolled wound-healing process in response to chronic liver injury. Liver damage generates an inflammatory reaction that activates hepatic stellate cells (HSC) that transdifferentiate from quiescent cells that control retinol metabolism to proliferative and migratory...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12271
更新日期：2015-10-01 00:00:00
abstract：:Impaired Ca2+ homeostasis and smooth muscle contractility co-exist in acute cholecystitis (AC) leading to gallbladder dysfunction. There is no pharmacological treatment for this pathological condition. Our aim was to evaluate the effects of melatonin treatment on Ca2+ signaling pathways and contractility altered by ch...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2007.00520.x
更新日期：2008-04-01 00:00:00
abstract：:Human placental mitochondria might be a significant source of NADPH- and iron-dependent production of reactive oxygen species (ROS). Preeclampsia is believed to be a consequence of overproduction of ROS in human placenta. The experimental results presented here show that melatonin inhibits NADPH- and iron-dependent li...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2010.00779.x
更新日期：2010-09-01 00:00:00
abstract：:Melatonin is known to regulate a variety of physiological processes including control of circadian rhythms, regulation of seasonal reproductive function, regulation of body temperature, and so forth. Accumulating evidence from in vitro and in vivo experiments using rodent and chicken has also suggested that melatonin ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2006.00410.x
更新日期：2007-04-01 00:00:00
abstract：:A study was carried out to determine the possible influence of melatonin on the proliferation of Kirkman-Robbins hepatoma cells in Syrian hamsters, both in vivo and in vitro. A highly significant inhibition of the proliferation of transplanted hepatoma cells was observed in vivo following melatonin administration (pro...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1992.tb00063.x
更新日期：1992-10-01 00:00:00
abstract：:Melatonin (MT), endogenously secreted by the pineal gland, is closely related to multiple biological processes; however, its effect on thrombopoiesis is still not well illustrated. Here, we demonstrate that MT administration can elevate peripheral platelet levels. Analysis of different stages in thrombopoiesis reveals...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12637
更新日期：2020-04-01 00:00:00
abstract：:The frequency of mitoses of adrenaline (A) cells and noradrenaline (N) cells in the adrenal medulla of nonoperated (NO), sham-operated (SPX), and pinealectomized (PX) male, 53-day-old Holtzman rats (n = 133) was investigated by means of light microscopy. Animals were killed at eight time points during a standardized 2...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1990.tb00803.x
更新日期：1990-01-01 00:00:00
abstract：:Carbon tetrachloride (CCl4) exerts its toxic effects by the generation of free radicals. In this study we investigated whether melatonin, a potent free radical scavenger, could prevent the deleterious effects of CCl4. Liver homogenates and liver microsomes were incubated with CCl4 in the presence of melatonin and lipi...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1995.tb00164.x
更新日期：1995-08-01 00:00:00
abstract：:In a recent study melatonin (N-acetyl-5-methoxytryptamine), a well-investigated animal molecule but minimally studied in plants, was seen to have a physiological role as growth-promoting molecule in lupin hypocotyls. In the present study, the role of melatonin as a growth promoter is extended to coleoptiles of canary ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2005.00226.x
更新日期：2005-09-01 00:00:00
abstract：:The effect of melatonin on thrombin-induced [3H]-arachidonic acid (AA) metabolism to cyclooxygenase derivatives was determined in platelets obtained from normal volunteers at 0830 and 2030 h. Percent conversion of radioactive AA was generally greater at 2030 h than at 0830 h for every cyclooxygenase derivative analyze...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1991.tb00465.x
更新日期：1991-10-01 00:00:00
abstract：:The known neuroprotective actions of melatonin could be due to its antioxidant or radical scavenging activity, or they could be due to specific interactions of the indole with its receptors. A study of structure-activity relationships may provide useful information when a validated macromolecular target has not been (...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1046/j.1600-079x.2003.00102.x
更新日期：2004-03-01 00:00:00
abstract：:Lethal oxidative stress was investigated in the dinoflagellate Gonyaulax polyedra by measuring the dying-peak of bioluminescence during circadian phases of low physiological light emission, low bioluminescence capacity, and low sensitivity to stimulatory agents. Measurements were carried out in constant darkness after...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1997.tb00353.x
更新日期：1997-11-01 00:00:00
abstract：:Oxidative stress is involved in ischemia-reperfusion injury and allograft rejection after transplantation. We studied two well-known antioxidants, melatonin and ascorbic acid (AA), in relation to the survival of a pancreas transplantation model without immunosuppression. Forty-eight Landrace pigs were divided into thr...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2011.00908.x
更新日期：2011-11-01 00:00:00
abstract：:By use of Phaseolus vulgaris-leucoagglutinin as an anterograde in vivo tracer, a direct projection from the dorsal raphe nucleus to the pineal complex of the rat was demonstrated. The nerve fibers extended from the dorsal raphe nucleus rostrally through the mesencephalic periaqueductal grey and entered the deep pineal...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1998.tb00381.x
更新日期：1998-08-01 00:00:00
abstract：:The aim of this study was to compare the circadian control of melatonin production in teleosts. To do so, the effects of ophthalmectomy on circulating melatonin rhythms were studied along with ex vivo pineal culture in six different teleosts. Results strongly suggested that the circadian control of melatonin productio...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2007.00480.x
更新日期：2007-11-01 00:00:00
abstract：:Aging induces changes in several organs and tissues, such as the liver, and this process might be due to oxidative damage caused by free radicals and inflammatory mediators. Melatonin is a secretory product with well-known antioxidant properties. The aim of this study was to investigate the effect of melatonin adminis...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2004.00199.x
更新日期：2005-05-01 00:00:00
abstract：:Obesity, a major risk factor for ischemic heart disease, is associated with increased oxidative stress and reduced antioxidant status. Melatonin, a potent free radical scavenger and antioxidant, has powerful cardioprotective effects in lean animals but its efficacy in obesity is unknown. We investigated the effects of...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2010.00826.x
更新日期：2011-03-01 00:00:00
abstract：:Our objective was to evaluate the maternal-fetal transfer of melatonin in pregnant women. Serum melatonin concentration was measured by high-performance liquid chromatography with electrochemical detection in a maternal vein and in the umbilical artery and umbilical vein at the time of birth. Blood samples were obtain...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1998.tb00550.x
更新日期：1998-10-01 00:00:00
abstract：:Respiratory activity is under circadian modulation and the physiological mechanisms may involve the pineal secretory product, melatonin, and the carotid chemoreceptor. We hypothesized that melatonin modulates the carotid chemoreceptor response to hypercapnic acidosis. To determine whether the effect of melatonin on th...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1046/j.1600-079x.2003.00094.x
更新日期：2004-01-01 00:00:00
abstract：:Glioblastoma stem-like cells (GSCs) displaying self-renewing and tumor-propagating capacity play a particularly important role in maintaining tumor growth, therapeutic resistance, and tumor recurrence. Therefore, new therapeutic strategies focusing on impairing GSC maintenance are urgently needed. Here, we used GSCs i...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12341
更新日期：2016-09-01 00:00:00
