Abstract:
:Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality. There have been no material advances in the treatment of preeclampsia for nearly 50 years. Combining in vitro studies and a clinical trial, we aimed to determine whether melatonin could be a useful adjuvant therapy. In a xanthine/xanthine oxidase (X/XO) placental explant model, melatonin reduced oxidative stress (8-isoprostane) and enhanced antioxidant markers (Nrf2 translocation, HO-1), but did not affect explant production of anti-angiogenic factors (sFlt, sEng, activin A). In cultured HUVECs, melatonin mitigated TNFα-induced vascular cell adhesion molecule expression and rescued the subsequent disruption to endothelial monolayer integrity but did not affect other markers for endothelial activation and dysfunction. In a phase I trial of melatonin in 20 women with preeclampsia, we assessed the safety and efficacy of melatonin on (i) preeclampsia progression, (ii) clinical outcomes, and (iii) oxidative stress, matching outcomes with recent historical controls receiving similar care. Melatonin therapy was safe for mothers and their fetuses. Compared to controls, melatonin administration extended the mean ± SEM diagnosis to delivery interval by 6 ± 2.3 days reduced the need for increasing antihypertensive medication on days 3-4 (13% vs 71%), days 6-7 (8% vs 51%), and at delivery (26% vs 75%). All other clinical and biochemical measures of disease severity were unaffected by melatonin. We have shown that melatonin has the potential to mitigate maternal endothelial pro-oxidant injury and could therefore provide effective adjuvant therapy to extend pregnancy duration to deliver improved clinical outcomes for women with severe preeclampsia.
journal_name
J Pineal Resjournal_title
Journal of pineal researchauthors
Hobson SR,Gurusinghe S,Lim R,Alers NO,Miller SL,Kingdom JC,Wallace EMdoi
10.1111/jpi.12508subject
Has Abstractpub_date
2018-10-01 00:00:00pages
e12508issue
3eissn
0742-3098issn
1600-079Xjournal_volume
65pub_type
杂志文章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::Previous research has shown that antioxidant (butylated hydroxyanisole) treatment ameliorates respiratory syncytial virus (RSV)-induced disease and lung inflammation. Melatonin has been reported to exhibit a wide varieties of biological effects, including antioxidant and anti-inflammation, and has no evident toxicity ...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2009.00733.x
更新日期:2010-03-01 00:00:00
abstract::Melatonin, a molecule produced in the pineal gland and retina of vertebrates, plays a major role in day-night circadian rhythms and other physiological processes, including the immune responses. Because little is known in this respect in fish, we have evaluated the in vivo role of melatonin in the main innate immune a...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2008.00557.x
更新日期:2008-08-01 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::The permeability of the pineal gland to lanthanum was investigated by means of transmission electron microscopy and X-ray microanalysis. Different pineal cell populations were studied. Light pinealocytes as well as glial cells were not permeated by the tracer lanthanum, which normally stays extracellularly. Dark pinea...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1992.tb00031.x
更新日期:1992-03-01 00:00:00
abstract::We tested the hypothesis that melatonin (Mel) enhances exogenous mitochondria (Mito) treatment against rodent hepatic ischemia-reperfusion (IR) injury. In vitro study utilized three groups of hepatocytes (i.e. nontreatment, menadione, and menadione-melatonin treatment, 4.0 × 10(5) each), while in vivo study used adult...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12326
更新日期:2016-08-01 00:00:00
abstract::Melatonin, a major pineal secretory product, exerts a range of physiological and neuroprotective effects. However, the functional significance of melatonin in determining neural identity, and the mechanisms by which this may occur, is unknown. In this study, P19 cells were used as a model system and cell behavior was ...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12153
更新日期:2014-09-01 00:00:00
abstract::When organic compounds are irradiated with UV light at 254 nm, part of their covalent bonds can dissociate if the compound absorbs light at that wavelength. Therefore, photo-degradation depends strongly on the wavelength used. The energy of a light quanta at 254 nm amounts to approximately 110 kcal/mol quanta, which i...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.2007.00536.x
更新日期:2008-05-01 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::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::Sirtuin 1 is a member of the sirtuin family of protein deacetylases, which have attracted considerable attention as mediators of lifespan extension in several model organisms. Induction of sirtuin 1 expression also attenuates neuronal degeneration and death in animal models of Alzheimer's disease and Huntington's dise...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2009.00706.x
更新日期:2009-10-01 00:00:00
abstract::GPR50 is an orphan seven transmembrane protein related to the melatonin receptor subfamily comprising MT(1) and MT(2) receptors. In the absence of any known ligand for GPR50, other tools are critical for the characterization of this protein. Here, we describe the generation, purification and characterization of the fi...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2007.00437.x
更新日期:2007-08-01 00:00:00
abstract::In the present research, we studied the effect of the administration of melatonin or S-adenosyl-L-methionine (S-AMe) on oxidative stress and hepatic cholestasis produced by double ligature of the extra-hepatic biliary duct (LBD) in adult male Wistar rats. Hepatic oxidative stress was evaluated by the changes in the am...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1034/j.1600-079x.2001.280303.x
更新日期:2000-04-01 00:00:00
abstract::Melatonin, an endogenous neurohormone secreted by the pineal gland, has a variety of physiological functions and neuroprotective effects. However, its protective role on the neural tube defects (NTDs) was not very clear. The aim of this study was to investigate the effects of melatonin on the incidence of NTDs (includ...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12282
更新日期:2015-11-01 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::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::The rod outer segment (ROSg) membranes are essentially lipoprotein complexes. Rhodopsin, the major integral protein of ROSg, is surrounded by phospholipids highly enriched in docosahexaenoic acid (22:6 n3). This fluid environment plays an important role for conformational changes after photo-activation. Thus, ROSg mem...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2006.00352.x
更新日期:2006-10-01 00:00:00
abstract::Recent investigations of our group established that melatonin modulates hormone secretion of pancreatic islets via melatonin receptor types MT1 and MT2. Expression of MT1 and MT2 has been shown in mouse, rat, and human pancreatic islets as well as in the β-, α-, and δ-cell lines INS-1, αTC1.9, and QGP-1. In view of th...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12480
更新日期:2018-08-01 00:00:00
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 cardio...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12263
更新日期:2015-10-01 00:00:00
abstract::Oxidative stress is reported as one of the most widely accepted mechanisms of maneb (MB)- and paraquat (PQ)-induced nigrostriatal dopaminergic neurodegeneration leading to the Parkinson's disease (PD) phenotype. The study investigated the effects of silymarin, an antioxidant of plant origin, and melatonin, an indoleam...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2010.00819.x
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journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2008.00600.x
更新日期:2009-01-01 00:00:00
abstract::The effect of anticonvulsant drugs on daytime and nighttime N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) levels was investigated. Some of the drugs caused a significant reduction in daytime NAT and HIOMT levels, possibly owing to beta-receptor blockade although other mechanisms cannot be exc...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1986.tb00740.x
更新日期:1986-01-01 00:00:00
abstract::The purpose of this study was to determine and compare the light sensitivity of two commercially important, phylogenetically different teleost species in terms of melatonin production. Three series of experiments were performed on both Atlantic salmon and European sea bass. First, a range of light intensities were tes...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2006.00330.x
更新日期:2006-08-01 00:00:00
abstract::Light and electron microscopic demonstrations for acid phosphatase (AcPase) activity in the chicken pineal gland were studied with special reference to the changes induced by the light-dark cycle. AcPase-positive lysosomes and Golgi cisternae and vesicles located in the pinealocyte in the light period are well develop...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1989.tb00407.x
更新日期:1989-01-01 00:00:00
abstract::Resistance inducers are a class of agrochemicals, including benzothiadiazole and chitosan, which activate the plant own defence mechanisms. In this work, open-field treatments with plant activators were performed on two red grape (Vitis vinifera L.) varieties cultivated in different localities, Groppello (Brescia, Lom...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2011.00887.x
更新日期:2011-10-01 00:00:00
abstract::Melatonin, a potent antioxidant, has shown to be beneficial in murine Venezuelan equine encephalomyelitis (VEE) virus infection. In addition, melatonin can induces the production of interleukin-1 beta (IL-1beta), a cytokine capable of inducing increased expression of inducible nitric oxide synthase; the activity of th...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2006.00381.x
更新日期:2007-03-01 00:00:00
abstract::The aim of the study was to determine whether a discrepancy between the genetically determined endogenous circadian period and an abnormally long Zeitgeber period disturbs the development of melatonin synthesis. Breeding pairs of rats were kept under 12:12- or 14:14-hr light:dark (LD) conditions. Pineal melatonin cont...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1996.tb00283.x
更新日期:1996-10-01 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::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::Melatonin is found in a wide variety of plant species. Several investigators have studied the physiological roles of melatonin in plants. However, its role is not well understood because of the limited information on its biosynthetic pathway. To clarify melatonin biosynthesis in plants, we isolated a cDNA-coded arylal...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2009.00673.x
更新日期:2009-05-01 00:00:00