Antioxidant Effect of Melatonin in Preterm Newborns

Marseglia, Lucia; Gitto, Eloisa; Laschi, Elisa; Giordano, Maurizio; Romeo, Carmelo; Cannavò, Laura; Toni, Anna Laura; Buonocore, Giuseppe; Perrone, Serafina

doi:10.1155/2021/6308255

Cited by 23 publications

(22 citation statements)

References 38 publications

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“…However, the design of this study used the radioimmunoassay method and not randomized premature infants based on birth weight. Deficiency of the powerful antioxidant melatonin was the basis for studying the effect of increasing in blood levels in premature infants by oral supplementation [17]. The study included 36 premature weighing more than 1700 g. However, outcomes have not been studied.…”

Section: Methodsmentioning

confidence: 99%

Urinary Melatonin Metabolite in Premature Infants with Extremely and Very Low Birth Weight

Kuzienkova¹,

Klymenko²

2022

Ukr. ž. med. bìol. sportu

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The aim. Determination of daily urinary 6-sulfatoxymelatonin in premature infants with extremely and very low birth weight. Materials and methods. A non-invasive, descriptive, single-centered study involving data of 96 premature infants with weight less than 1500 g : 46 infants with extremely and 50 infants with very low birth weight. The study included a detailed scrutiny of history and objective examinations, data from medical records, anthropometric measurements, and daily urine collection. Determination of 6 - SM in the 24-hours urine collection from premature infants was performed by enzyme immunoassay on the analyzer “Labline-90” (Austria) using a commercial test system manufactured by “LDR” (LABOR DIAGNOSTIKA NORD GmbH & Co.KG, Germany) according to the provided instruction. 166 portions of urine were collected during the examination in time intervals: 96 portions of urine in premature infants at 1st day of life and 70 portions at 10th – 14th day of life. Results. Ante- and intranatal periods for the infants enrolled in the study were characterized by conditions: premature rupture of membranes 37 (38.5%), multiple pregnancy 16 (16.6%), preeclampsia 15 (15.6%), isthmic-cervical insufficiency 11 (11.5%), placental abruption 8 (8.3%), extra corporal fertilization 5 (5.2%), chorioamnionitis 4 (4.2%); caesarean section urgent 33 (34.4%) and planned 24 (25.0%). There was no any significant difference in frequency of ante – and intranatal pathology between ELBW and VLBW. Antenatal administration of corticosteroids for reduce the severity of neonatal respiratory distress syndrome occurred in all mothers of infants enrolled in the study. There was significant low urinary 6-sulfatoxymelatonin level in extremely low birth weight infants (median 120.0 pg /mL) on the 1st day of life compared with very low birth weight (median 348.5 pg / mL). There was no difference at 10 – 14th days. The predictive level of lethal outcome in infants with extremely low birth weight is ≤ 84 pg / mL with sensitivity 84.62% and specificity 70.0%. Conclusion. In infants with extremely and very low birth weight the determining the urinary 6-sulfatoxymelatonin is a non-invasive method. The significant decrease level of urinary 6-sulfatoxymelatonin in infants with extremely low birth weight on the first day of life was found. The measurement of urinary 6-sulfatoxymelatonin will allow to establish the prediction of perinatal outcomes. Its levels <87 pg / mL is associated with lethal outcomes. Authors speculate than it will the way for future supplement of melatonin to premature infants and study of its effect on perinatal outcomes

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Section: Methodsmentioning

confidence: 99%

Urinary Melatonin Metabolite in Premature Infants with Extremely and Very Low Birth Weight

Kuzienkova¹,

Klymenko²

2022

Ukr. ž. med. bìol. sportu

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“…Complementary adjunctive and immunomodulatory therapies are required to reverse immune system dysfunction and cytokine dysregulation. Melatonin is also known to have anti-inflammatory [ 15 ], antioxidant [ 16 ], immunomodulatory [ 17 ] and antiviral [ 18 ] infectious activities. It may be useful to use melatonin together with REGN-COV2 in elderly and other high-risk patients as an adjuvant to vaccines against the Omicron variant of SARS-CoV-2infection.…”

Section: Introductionmentioning

confidence: 99%

Melatonin and REGN-CoV2 combination as a vaccine adjuvant for Omicron variant of SARS-CoV-2

et al. 2022

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The omicron variant (B.529) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in late 2021, caused panic worldwide due to its contagiousness and multiple mutations in the spike protein compared to the Delta variant (B.617.2). There is currently no specific antiviral available to treat Coronavirus disease 2019 (COVID-19). However, studies on neutralizing monoclonal antibodies (mAb) developed to fight COVID-19 are growing and gaining traction. REGN-COV2 (Regeneron or imdevimab-casirivimab combination), which has been shown in recent studies to be less affected by Omicron's RBD (receptor binding domain) mutations among other mAb cocktails, plays an important role in adjuvant therapy against COVID-19. On the other hand, it is known that melatonin, which has antioxidant and immunomodulatory effects, can prevent a possible cytokine storm, and other severe symptoms that may develop in the event of viral invasion. Along with all these findings, we believe it is crucial to evaluate the use of melatonin with REGN-COV2, a cocktail of mAbs, as an adjuvant in the treatment and prevention of COVID-19, particularly in immunocompromised and elderly patients.

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“…Nevertheless, the low effectiveness of hypothermia is a driving force for the urgent development of adjunct pharmaceutical agents 1 . Melatonin, a hormone well known for its involvement in the circadian rhythm, was tested in preclinical trials for perinatal NE and demonstrated neuroprotective effects by pleiotropic and immunomodulatory mechanisms 2–4 . Moreover, our group was the first to define the pharmacokinetic profile of 0.5 mg/kg melatonin given orally over 4 h. This dosage was given to five neonates with NE undergoing therapeutic hypothermia.…”

Section: Introductionmentioning

confidence: 99%

“…1 Melatonin, a hormone well known for its involvement in the circadian rhythm, was tested in preclinical trials for perinatal NE and demonstrated neuroprotective effects by pleiotropic and immunomodulatory mechanisms. [2][3][4] Moreover, our group was the first to define the pharmacokinetic profile of 0.5 mg/kg melatonin given orally over 4 h. This dosage was given to five neonates with NE undergoing therapeutic hypothermia. The highest plasma concentration occurred between 3 and 12 h after the completion of the infusion, which was a longer half-life to compare animals and human adults.…”

Section: Introductionmentioning

confidence: 99%

Human–rat integrated microRNAs profiling identified a new neonatal cerebral hypoxic–ischemic pathway melatonin‐sensitive

Weiss

Carloni

Vanzolini

et al. 2022

Journal of Pineal Research

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Neonatal encephalopathy (NE) is a pathological condition affecting long‐term neurodevelopmental outcomes. Hypothermia is the only therapeutic option, but does not always improve outcomes; hence, researchers continue to hunt for pharmaceutical compounds. Melatonin treatment has benefitted neonates with hypoxic–ischemic (HI) brain injury. However, unlike animal models that enable the study of the brain and the pathophysiologic cascade, only blood is available from human subjects. Therefore, due to the unavailability of neonatal brain tissue, assumptions about the pathophysiology in pathways and cascades are made in human subjects with NE. We analyzed animal and human specimens to improve our understanding of the pathophysiology in human neonates. A neonate with NE who underwent hypothermia and enrolled in a melatonin pharmacokinetic study was compared to HI rats treated/untreated with melatonin. MicroRNA (miRNA) analyses provided profiles of the neonate's plasma, rat plasma, and rat brain cortexes. We compared these profiles through a bioinformatics tool, identifying Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways common to HI brain injury and melatonin treatment. After evaluating the resulting pathways and the literature, to validate the method, the key proteins expressed in HI brain injury were investigated using cerebral cortexes. The upregulated miRNAs in human neonate and rat plasma helped identify two KEGG pathways, glioma and long‐term potentiation, common to HI injury and melatonin treatment. A unified neonatal cerebral melatonin‐sensitive HI pathway was designed and validated by assessing the expression of protein kinase Cα (PKCα), phospho (p)‐Akt, and p‐ERK proteins in rat brain cortexes. PKCα increased in HI‐injured rats and further increased with melatonin. p‐Akt and p‐ERK returned phosphorylated to their basal level with melatonin treatment after HI injury. The bioinformatics analyses validated by key protein expression identified pathways common to HI brain injury and melatonin treatment. This approach helped complete pathways in neonates with NE by integrating information from animal models of HI brain injury.

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Antioxidant Effect of Melatonin in Preterm Newborns

Cited by 23 publications

References 38 publications

Urinary Melatonin Metabolite in Premature Infants with Extremely and Very Low Birth Weight

Urinary Melatonin Metabolite in Premature Infants with Extremely and Very Low Birth Weight

Melatonin and REGN-CoV2 combination as a vaccine adjuvant for Omicron variant of SARS-CoV-2

Human–rat integrated microRNAs profiling identified a new neonatal cerebral hypoxic–ischemic pathway melatonin‐sensitive

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