Effects of Melatonin on Blood Pressure, Oxidative Stress and Placental Expressions of TNFα, IL-6, VEGF and sFlt-1 in RUPP Rat Model of Preeclampsia

Uzun, Metehan; Gencer, Meryem; Türkön, Hakan; Öztopuz, Özlem; Demir, Ufuk; Ovalı, Mehmet Akif

doi:10.1016/j.arcmed.2017.08.007

Cited by 19 publications

(16 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In RUPP animals, a pregnant rat model presenting reduced uterine blood flow by using abdominal aorta and ovarian artery clipping, aggravating conditions such as hypertension, proteinuria, and failure in renal functions are present. A study by Uzun et al [92] revealed that pinealectomy intensified these effects observed in RUPP animals (e.g., reducing VEGF, TNF-α, and total antioxidant status and enhancing oxidative stress index and soluble fms-like tyrosine kinase 1 (sFlt-1) expression) while treatment with melatonin reduced blood pressure (via nitric oxide pathway) and placental expression of sFlt-1; these findings may help in determining not only the melatonin effects but how melatonin deficiency influences preeclampsia. To strengthen these findings, an in vitro assay using placental explants from normal term pregnancy (>38 weeks) revealed that melatonin (100-1000 µM) potentiated the antioxidant response by upregulating the expression of thioredoxin, glutamate-cysteine ligase, and NADPH: quinone acceptor oxidoreductase 1 in the placenta while reducing sFlt-1 secretion from primary trophoblast without altering the genes related to endothelial dysfunction [93].…”

Section: The Beneficial Effects Of Melatonin On Placental Tissue: a Lmentioning

confidence: 99%

“…Preeclampsia has been studied experimentally [92,93]. In RUPP animals, a pregnant rat model presenting reduced uterine blood flow by using abdominal aorta and ovarian artery clipping, aggravating conditions such as hypertension, proteinuria, and failure in renal functions are present.…”

Section: The Beneficial Effects Of Melatonin On Placental Tissue: a Lmentioning

confidence: 99%

“…Pregnancy loss is associated with immunological disturbances and oxidative stress; in this perspective, melatonin serves as a direct free-radical scavenger possessing immunomodulatory properties [97]. The precise mechanism by which the fetus escapes immune rejection by the mother remains inconclusive; however, there is increasing evidence that associates the circadian clock and melatonin with pregnancy and synchronous programming of the immune system [92]. Melatonin is rhythmically produced by the placental cells and is related to lymphocyte proliferation and cytokine production [78,98].…”

Section: Melatonin's Action On the Immune Microenvironment At The Matmentioning

confidence: 99%

See 2 more Smart Citations

Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms

Chuffa

Lupi

Cucielo

et al. 2019

IJMS

View full text Add to dashboard Cite

The development of the endometrium is a cyclic event tightly regulated by hormones and growth factors to coordinate the menstrual cycle while promoting a suitable microenvironment for embryo implantation during the “receptivity window”. Many women experience uterine failures that hamper the success of conception, such as endometrium thickness, endometriosis, luteal phase defects, endometrial polyps, adenomyosis, viral infection, and even endometrial cancer; most of these disturbances involve changes in endocrine components or cell damage. The emerging evidence has proven that circadian rhythm deregulation followed by low circulating melatonin is associated with low implantation rates and difficulties to maintain pregnancy. Given that melatonin is a circadian-regulating hormone also involved in the maintenance of uterine homeostasis through regulation of numerous pathways associated with uterine receptivity and gestation, the success of female reproduction may be dependent on the levels and activity of uterine and placental melatonin. Based on the fact that irregular production of maternal and placental melatonin is related to recurrent spontaneous abortion and maternal/fetal disturbances, melatonin replacement may offer an excellent opportunity to restore normal physiological function of the affected tissues. By alleviating oxidative damage in the placenta, melatonin favors nutrient transfer and improves vascular dynamics at the uterine–placental interface. This review focuses on the main in vivo and in vitro functions of melatonin on uterine physiological processes, such as decidualization and implantation, and also on the feto-maternal tissues, and reviews how exogenous melatonin functions from a mechanistic standpoint to preserve the organ health. New insights on the potential signaling pathways whereby melatonin resists preeclampsia and endometriosis are further emphasized in this review.

show abstract

Section: The Beneficial Effects Of Melatonin On Placental Tissue: a Lmentioning

confidence: 99%

Section: The Beneficial Effects Of Melatonin On Placental Tissue: a Lmentioning

confidence: 99%

Section: Melatonin's Action On the Immune Microenvironment At The Matmentioning

confidence: 99%

See 1 more Smart Citation

Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms

Chuffa

Lupi

Cucielo

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…Furthermore, in the L‐NAME‐induced hypertensive rats, melatonin slightly reduces blood pressure and increases aortic NOS activity but is unable to prevent impaired ACh‐mediated relaxation of femoral arteries . Furthermore, melatonin treatment reduces mean arterial pressure and increases circulating levels of VEGF in pinealectomized RUPP rats . These effects are thought to be due to increases in NO availability.…”

Section: Targeting Oxidative Stressmentioning

confidence: 99%

Targeting the vascular dysfunction: Potential treatments for preeclampsia

et al. 2019

View full text Add to dashboard Cite

Preeclampsia is a pregnancy-specific disorder clinically characterized by new-onset hypertension (>20 weeks' gestation) with one or more of proteinuria and maternal organ dysfunction such as renal insufficiency, liver dysfunction, neurological complications, fetal growth restriction, or uteroplacental dysfunction. 1,2 Each year, preeclampsia is the principal cause of death in over 60 000 women and in more than 500 000 babies globally. 3 The pathophysiological mechanisms underlying the disease are still not entirely clear. Briefly, In 2017, Sarah was awarded her PhD at the University of Melbourne, Australia, and is currently an NHMRC Peter Doherty Research Fellow in the Department of Obstetrics and Gynecology at Monash University, Australia. The focus of her research is to assess the potential of new and old therapeutics to target the vascular dysfunction of preeclampsia, and translate these studies into clinical application. AbstractPreeclampsia is a pregnancy-specific disorder, primarily characterized by new-onset hypertension in combination with a variety of other maternal or fetal signs. The pathophysiological mechanisms underlying the disease are still not entirely clear.Systemic maternal vascular dysfunction underlies the clinical features of preeclampsia. It is a result of oxidative stress and the actions of excessive anti-angiogenic factors, such as soluble fms-like tyrosine kinase, soluble endoglin, and activin A, released by a dysfunctional placenta. The vascular dysfunction then leads to impaired regulation and secretion of relaxation factors and an increase in sensitivity/production of constrictors. This results in a more constricted vasculature rather than the relaxed vasodilated state associated with normal pregnancy. Currently, the only effective "treatment" for preeclampsia is delivery of the placenta and therefore the baby.Often, this means a preterm delivery to save the life of the mother, with all the attendant risks and burdens associated with fetal prematurity. To lessen this burden, there is a pressing need for more effective treatments that target the maternal vascular dysfunction that underlies the hypertension. This review details the vascular effects of key drugs undergoing clinical assessment as potential treatments for women with preeclampsia.

show abstract

“…During pregnancy, there are two main pathways through which melatonin plays its functions: the systemic release has a role in programming the circadian rhythmicity of the near-term uterus, by acting synergically with oxytocin in delivery, and in promoting fetal development 12,13 ; the local release exerts antioxidant functions with melatonin acting as a direct free radicals' scavenger and also through its stimulation of other antioxidant enzymes and the reduction of anti-angiogenic factors and pro-inflammatory molecules 9,14 . Therefore, the local production of melatonin seems to have an important role in preserving placental homeostasis and, as shown in animal models, oral supplementation with melatonin reduces blood pressure, increases the production of angiogenic factors, increases the uterine arterial flow and the total serum antioxidant capacity 15,16 . Such function could be helpful in placental insufficiency-related disorders, like preeclampsia (PE) and fetal growth restriction (FGR), characterised by increased oxidative stress and pro-inflammatory status 1 .…”

Section: Introductionmentioning

confidence: 99%

The role of melatonin in pregnancies complicated by placental insufficiency: a systematic review

Fantasia¹,

Bussolaro²,

Stampalija³

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Pregnancies complicated by placental insufficiency are characterised by increased oxidative stress. It has been suggested that melatonin has antioxidant properties and contributes to the maintenance of placental homeostasis. Objective: To systematically review the available literature about melatonin in pregnancies complicated by placental insufficiency, specifically preeclampsia and fetal growth restriction, exploring three different aspects: 1) maternal melatonin levels; 2) expression and activity of melatonin placental receptors; 3) effects of maternal melatonin administration. Search strategy: PubMed (Medline) and Scopus were searched until December 2020. Selection criteria: Published literature in English language describing the role of melatonin in pregnancies complicated by placental insufficiency, with a specific focus on preeclampsia and fetal growth restriction. Data collection and analysis: Identified studies were screened and assessed independently by two authors. Data were extracted and compiled in a qualitative evidence synthesis. Main results: Pregnancies complicated by placental insufficiency show a significant reduction in maternal systemic serum melatonin levels and a significant reduction in the expression of placental melatonin receptors. Melatonin administration in pregnancy seems safe and may reduce oxidative stress. Conclusion: The circadian pattern of melatonin secretion seems to be altered in pregnancies complicated by placental insufficiency. This is reflected by lower production of melatonin, with consequent lower systemic and placental concentrations, and lower expression of melatonin receptors, thus reducing the local release of the indole and its autocrine function. Funding: None Keywords: Melatonin, Preeclampsia, Fetal growth restriction, Placental insufficiency, Review.

show abstract

Effects of Melatonin on Blood Pressure, Oxidative Stress and Placental Expressions of TNFα, IL-6, VEGF and sFlt-1 in RUPP Rat Model of Preeclampsia

Cited by 19 publications

References 44 publications

Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms

Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms

Targeting the vascular dysfunction: Potential treatments for preeclampsia

The role of melatonin in pregnancies complicated by placental insufficiency: a systematic review

Contact Info

Product

Resources

About