Abstract：
:Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure, which leads to right ventricular (RV) hypertrophy and failure. The pathophysiological mechanisms of PH remain unclear but oxidative stress is believed to contribute to RV dysfunction. Melatonin is a powerful antioxidant and is cardioprotective against ischemia-reperfusion injury and hypertension. Therefore, we hypothesized that a chronic treatment with melatonin, given as a curative or preventive therapy, may confer cardiovascular benefits in PH. PH was induced in Long Evans rats (n ≥ 6 per group), with a single subcutaneous injection of monocrotaline (MCT, 80 mg/kg). Melatonin was given daily in the drinking water, with the treatment starting either on the day of the injection of MCT (dose testing: melatonin 75 ng/L and 6 mg/kg), 14 days after the injection of MCT (curative treatment: 6 mg/kg), or 5 days before the injection (preventive treatment: 6 mg/kg). The development of PH was assessed by measuring RV hypertrophy, RV function, cardiac interstitial fibrosis, and plasma oxidative stress. Compared with controls, MCT-treated rats displayed RV hypertrophy and dysfunction, increased interstitial fibrosis, and elevated plasma oxidative stress. A chronic melatonin treatment (75 ng/L or 6 mg/kg) reduced RV hypertrophy, improved RV function and reduced plasma oxidative stress. Curative and preventive treatment improved RV functional and plasma oxidative stress parameters and reduced cardiac interstitial fibrosis. Our data demonstrate that melatonin confers cardioprotection in this model of PH. As melatonin is an inexpensive and safe drug, we propose that clinical investigation of the effects of melatonin on RV function in patients with PH should be considered.
journal_name
J Pineal Resjournal_title
Journal of pineal researchauthors
Maarman G,Blackhurst D,Thienemann F,Blauwet L,Butrous G,Davies N,Sliwa K,Lecour Sdoi
10.1111/jpi.12263subject
Has Abstractpub_date
2015-10-01 00:00:00pages
343-53issue
3eissn
0742-3098issn
1600-079Xjournal_volume
59pub_type
杂志文章abstract：:Djungarian hamsters kept in long photoperiod (16:8 L:D) were injected daily at 0800, 1200, or 1600 with 25 micrograms of melatonin. During 90 days of treatment, body weight and fur coloration were checked at weekly intervals, and at the end of the treatment the reproductive status of the hamsters and their thermoregul...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1985.tb00719.x
更新日期：1985-01-01 00:00:00
abstract：:Melatonin has shown particular promise as a neuroprotective agent to prevent motoneuron death in animal models of both amyotrophic lateral sclerosis (ALS) and spinal cord injuries (SCI). However, an understanding of the roles of endogenous melatonin receptors including MT1, MT2, and orphan G-protein receptor 50 (GPR50...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2012.01022.x
更新日期：2013-01-01 00:00:00
abstract：:The presence of melatonin and the enzymes (transcripts and activities) involved in its synthesis, i.e. arylalkylamine N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), was investigated in the eggs and early embryos of Japanese quail at Hamburger-Hamilton stages 1-10. Melatonin was present in ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2007.00421.x
更新日期：2007-04-01 00:00:00
abstract：:The protective role of exogenous melatonin on U-induced nephrotoxicity was investigated in rats. Animals were given single doses of uranyl acetate dihydrate (UAD) at 5 mg/kg (subcutaneous), melatonin at 10 or 20 mg/kg (intraperitoneal), and UAD (5 mg/kg) plus melatonin (10 or 20 mg/kg), or vehicle (control group). In ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2007.00447.x
更新日期：2007-08-01 00:00:00
abstract：:Excessive activity of NADPH oxidase (Nox) is considered to be of importance for the progress of diabetic nephropathy. The aim of the study was to elucidate the effect of melatonin, known for its nephroprotective properties, on Nox activity under diabetic conditions. The experiments were performed on three groups of an...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12296
更新日期：2016-01-01 00:00:00
abstract：:Experiments were designed to test the hypothesis that the pineal gland mediates the effects of changing day length and thereby synchronizes implantation within the population of spotted skunks. Intact, sham-superior cervical ganglionectomized (SCGx), SCGx, and SCGx/bilateral orbitally enucleated (B1) pregnant skunks w...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1986.tb00720.x
更新日期：1986-01-01 00:00:00
abstract：:Five adult pasture-bred Prim Holstein cows were used to document the time invariance of melatonin disposition in the cow. Melatonin was administered by an intravenous route as a bolus (5 micrograms/kg of body weight) at either 1430 or 2230. Data were analysed according to a three-compartment open model with melatonin ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1993.tb00521.x
更新日期：1993-10-01 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：:Excessive production of nitric oxide (NO) may play a detrimental role in the process of hypoxia-related neuropathology. This study explored whether treatment with melatonin would attenuate the neuropathological changes in the vagal ganglia following a severe hypoxic insult. Thirty minutes prior to hypoxia treatment, y...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1034/j.1600-079x.2002.1816.x
更新日期：2002-03-01 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：:Classical anticancer therapies often are ineffective in patients with malignant glioma who have a survival of <1 year. Our previous studies showed a potent inhibitory effect of melatonin on glioma cell proliferation. This effect seems to be mediated by the well-known antioxidant properties of this molecule and the neg...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2007.00468.x
更新日期：2007-10-01 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：:No previous reports have described the effects of an increase in endogenous melatonin levels on plant yield and reproduction. Here, the phenotypes of melatonin-rich transgenic rice plants overexpressing sheep serotonin N-acetyltransferase were investigated under field conditions. Early seedling growth of melatonin-ric...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12129
更新日期：2014-05-01 00:00:00
abstract：:Experiments were conducted to determine whether daily melatonin injections could influence reentrainment of circadian locomotor activity rhythms in male Long-Evans rats after phase shifts of the light dark (LD) cycle. When exposed to a 5-h advance of the LD cycle, six out of 15 rats injected daily with melatonin at th...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1988.tb00782.x
更新日期：1988-01-01 00:00:00
abstract：:Previous data have demonstrated that a single 1-hr light pulse at night affects the secretion of melatonin in the ram if it was given at the appropriate time. This paper reports the effect on melatonin secretion of a 1-hr light pulse given at two different times at night to two groups of rams kept in constant darkness...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1996.tb00289.x
更新日期：1996-11-01 00:00:00
abstract：:Despite high in-hospital mortality associated with acute respiratory distress syndrome (ARDS), there is no effective therapeutic strategy. We tested the hypothesis that combined melatonin-mitochondria treatment ameliorates 100% oxygen-induced ARDS in rats. Adult male Sprague-Dawley rats (n = 40) were equally categoriz...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12199
更新日期：2015-03-01 00:00:00
abstract：:Epigenetic alterations have emerged as an important mechanism involved in tumorigenesis. The epigenetic impact of DNA methylation in various types of human cancer is not completely understood. Previously, we observed melatonin-induced differential expression of miRNA and miRNA-related genes in human breast cancer cell...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2012.01027.x
更新日期：2013-01-01 00:00:00
abstract：:Bisphenol A (BPA) has been reported to adversely affect the mammalian reproductive system in both sexes. However, the underlying mechanisms regarding how BPA disrupts the mammalian oocyte quality and how to prevent it have not been fully defined. Here, we document that BPA weakens oocyte quality by impairing both oocy...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12396
更新日期：2017-04-01 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：:The present study analyzes the participation of pineal stalk and superior cervical ganglia (SCG) in the conduction of photic evoked potentials (PEP) to the pineal body (PB) in unanesthetized freely moving rats implanted with semimicroelectrodes. The PEPs were recorded in PB, lateral hypothalamus (LH), and habenular co...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1987.tb00866.x
更新日期：1987-01-01 00:00:00
abstract：:The effect of light on melatonin biosynthesis was examined in detached rice (Oryza sativa cv. Asahi) leaves during the senescence process. The detached leaves were exposed to senescence treatment either in constant darkness or in constant light, and subjected to HPLC analysis for melatonin and its precursors. Higher m...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2012.00976.x
更新日期：2012-08-01 00:00:00
abstract：:The aim of this study was to investigate the localization in the superior cervical ganglia (SCG) of neuropeptide Y-containing neurons innervating the pineal gland. Following injection of the fluorescent tracer Fluoro-Gold (FG) into the superficial part of the pineal gland and retrograde axonal transport, labeled cells...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1989.tb00426.x
更新日期：1989-01-01 00:00:00
abstract：:Studies on farm animals have contributed significantly to our increased understanding of basic melatonin-related physiological mechanisms, as well as to the regulation of reproduction and pelage in individual domestic species. This review concentrates on recent work on the role of melatonin in the regulation of porcin...
journal_title：Journal of pineal research
pub_type： 杂志文章,评审
doi：10.1111/j.1600-079x.1994.tb00097.x
更新日期：1994-05-01 00:00:00
abstract：:The effect of melatonin injection on Freund's adjuvant-induced changes in levels and 24-hr rhythms of circulating ACTH, growth hormone (GH), prolactin (PRL), luteinizing hormone (LH), and insulin was assessed in rats. Animals received subcutaneous (s.c.) injections of melatonin (30 microg) or vehicle, 1 hr before ligh...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1999.tb00592.x
更新日期：1999-08-01 00:00:00
abstract：:Melatonin protects cells against various types of oxidative stress-induced apoptosis due primarily to its ability to effectively scavenge pathological and disease condition-augmented generation of mitochondrial reactive oxygen species (mROS). Once produced, mROS indiscriminately damage mitochondrial components and mor...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2009.00721.x
更新日期：2010-01-01 00:00:00
abstract：:In chronically inflamed animals, adrenal hormones exert a positive control on the secretion of melatonin by the pineal gland. In this paper, the mechanism of corticosterone as a modulator of melatonin and N-acetylserotonin (NAS) was determined. Rat pineal glands in culture, stimulated for 5 hr with noradrenaline (10 n...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2004.00191.x
更新日期：2005-04-01 00:00:00
abstract：:It is well established that some agents such as aminoglycosides generate free oxygen radicals, leading to an increased oxireductase production, which in turn increases tissue toxicity. The aim of this study is to test whether melatonin, the chief secretory product of the pineal gland and a highly effective antioxidant...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1034/j.1600-079x.2003.00059.x
更新日期：2003-09-01 00:00:00
abstract：:A decrease in nocturnal serum melatonin levels was reported in patients with clinically uncharacterized coronary artery disease. To assess whether there was a correlation between melatonin production and disease stage, we measured the nocturnal urinary excretion of 6-sulphatoxymelatonin (an index of blood melatonin co...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1034/j.1600-079x.2000.290302.x
更新日期：2000-10-01 00:00:00
abstract：:Incorporation of new therapeutic agents remains as a major challenge for treatment of patients with malignant haematological disorders. Melatonin is an indolamine without relevant side effects. It has been shown previously to exhibit synergism with several chemotherapeutic drugs in Ewing sarcoma cells by potentiating ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2010.00850.x
更新日期：2011-04-01 00:00:00
abstract：:In this study, the effect of melatonin on sodium arsenite (arsenite)-induced peripheral neurotoxicity was investigated using dorsal root ganglion (DRG) explants. After 24-hr incubation, arsenite (30 microm) consistently elevated the expression of heat shock protein 70 and haeme oxygenase-1, two well-known stress prote...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2008.00629.x
更新日期：2009-01-01 00:00:00
