scholarly journals Antioxidant Effect of Melatonin in Preterm Newborns

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Lucia Marseglia ◽  
Eloisa Gitto ◽  
Elisa Laschi ◽  
Maurizio Giordano ◽  
Carmelo Romeo ◽  
...  

Introduction. Preterm infants are at risk of free radical-mediated diseases from oxidative stress (OS) injury. Increased free radical generation has been demonstrated in preterm infants during the first seven days of life. Melatonin (MEL) is a powerful antioxidant and scavenger of free radicals. In preterm neonates, melatonin deficiency has been reported. Exogenous melatonin administration appears a promising strategy in the treatment of neonatal morbidities in which OS has a leading role. Objective. The aim was to evaluate plasma MEL concentrations and OS biomarkers in preterm newborns after early administration of melatonin. Methods. A prospective, randomized double-blind placebo-controlled pilot study was conducted from January 2019 to September 2020. Thirty-six preterm newborns were enrolled. Starting from the first day of life, 21 received a single dose of oral melatonin 0.5 mg/kg once a day, in the morning (MEL group); 15 newborns received an equivalent dose of placebo (placebo group). Samples of 0.2 mL of plasma were collected at 24 and 48 hours after MEL administration. Plasma concentrations of melatonin, non-protein-bound iron (NPBI), advanced oxidation protein products (AOPP), and F2-isoprostanes (F2-Isopr) were measured. Babies were clinically followed until discharge. Results. At 24 and 48 hours after MEL administration, the MEL concentrations were significantly higher in the MEL group than in the placebo group ( 52759.30 ± 63529.09 vs. 28.57 ± 46.24  pg/mL and 279397.6 ± 516344.2 vs. 38.50 ± 44.01  pg/mL, respectively). NPBI and AOPP did not show any statistically significant differences between the groups both at 24 and 48 hours. At 48 hours, the mean blood concentrations of F2-Isopr were significantly lower in the MEL group than in the placebo group ( 36.48 ± 33.85  pg/mL vs. 89.97 ± 52.01  pg/mL). Conclusions. Early melatonin administration in preterm newborns reduces lipid peroxidation in the first days of life showing a potential role to protect high-risk newborns. Trial Registration. This trial is registered with NCT04785183, Early Supplementation of Melatonin in Preterm Newborns: the Effects on Oxidative Stress.

2021 ◽  
Author(s):  
Rita Luciano ◽  
Domenico Marco Romeo ◽  
Giuseppina Mancini ◽  
Serena Sivo ◽  
Carolina Dolci ◽  
...  

Abstract ObjectiveLate-preterm infants (LPT) are at increased risk for long-term neurodevelopmental sequelaeand iron deficiency. Aim of the study is to assess the positive effect of iron supplementation on neurological development in healthy LPT.DesignWe designed a perspective, randomized placebo-controlled double-blind trial. The newborns were randomized in two groups: thirty-three patients received martial prophylaxis, thirty-three placebo. Every patient was assessed using the Griffith Mental Development Scales (GMDS)-II edition at 12 months of post-conceptional age.SettingThe study was performed at the Neonatology Unit of Fondazione Policlinico Gemelli IRCCS.PatientsSixty-six healthy LPT infants born between 340⁄7 and 366⁄7 weeks of Gestational Age were enrolled in the study.InterventionsOne group received martial prophylaxis from the third week of life to six months of post-conceptional age (2 mg/kg/day of iron pidolate), the other received placebo.Main outcome measuresFifty-two of the enrolled infants were assessed using the GMDS at 12-month of post-conceptional age. Statistical analysis of the mean scores of the Griffith subscales was performed.ResultsThere was a difference in the mean Developmental Quotient (DQ) (p<0.01) between the two groups: Iron Group mean DQ 121.45+10.53 vs Placebo Group mean DQ 113.25+9.70. Moreover, mean scores of the Griffith subscales A, B and D showed significant differences between the two Groups (scale A p<0.05, scale B p<0.02, scale D p<0.01 respectively).ConclusionsOur data show that newborns who received iron supplementation during the first six months of life achieved significantly better neurological outcomes at GMDS than Placebo group.


1997 ◽  
Vol 43 (7) ◽  
pp. 1196-1202 ◽  
Author(s):  
Cristine A Costa ◽  
Gilmar C Trivelato ◽  
Adriana M P Pinto ◽  
Etelvino J H Bechara

Abstract 5-Aminolevulinic acid (ALA), a heme precursor accumulated in acute intermittent porphyria and lead poisoning, undergoes metal-catalyzed aerobic oxidation at physiological pH to yield reactive free radical species (O2−·&gt;, HO·, and ALA·). We analyzed the relationships between plasma ALA concentrations, blood concentrations of lead, protoporphyrin IX (PP-IX), superoxide dismutase (SOD), and methemoglobin (metHb), and urine chemiluminescence (CL) in samples collected from lead-exposed workers. All variables measured were substantially (P &lt;0.01) higher (2–8-fold) in the lead-exposed workers (n = 60). Plasma ALA concentrations were, on average, 6-fold higher in lead-exposed workers. We observed positive linear relationships between ALA and lead (r = 0.992), ALA and PP-IX (r = 0.891), ALA and metHb (r = 0.984), lead and SOD (r = 0.948), ALA and urine CL (r = 0.987), and lead and PP-IX (r = 0.993). These data are consistent with our free radical hypothesis for lead poisoning, where ALA distribution to and accumulation in several organs may trigger oxidative stress responses.


2000 ◽  
pp. 593-599 ◽  
Author(s):  
JO Jorgensen ◽  
AM Rosenfalck ◽  
S Fisker ◽  
B Nyholm ◽  
MS Fineman ◽  
...  

OBJECTIVE: Hyperinsulinemia in association with GH excess is considered a compensatory response to insulin resistance, but the possibility of alternative insulinotropic mechanisms has not been investigated in vivo. It is also unknown how GH influences the secretion from pancreatic beta-cells of amylin, a peptide which regulates prandial glucose homeostasis and may be linked to development of beta-cell dysfunction. We therefore measured plasma concentrations of two gut insulinotropic hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulin-releasing peptide (GIP), and total as well as non-glycosylated amylin, in 24 GH-deficient adults before and after 4 months of GH replacement (daily evening injections of 2 IU GH/m). DESIGN: Double-blind, placebo-controlled, parallel study. METHODS: All participants underwent an oral glucose tolerance test (OGTT) at 0 and 4 months. RESULTS: A 33% suppression of fasting GLP-1 concentrations was measured in the GH group at 4 months (P=0.02), whereas a non-significant increase occurred in the placebo group (P=0.08). Fasting levels of GIP and amylin did not change significantly after 4 months in either group. The incremental response in GLP-1 during the OGTT was significantly lower after GH treatment as compared with both baseline (P=0.02) and the response in the placebo group (P=0. 03). The stimulation of GIP secretion following OGTT was similar on all occasions. The OGTT-induced incremental response in non-glycosylated amylin was moderately elevated after GH treatment as compared with placebo (P=0.05). Plasma concentrations of glucose and insulin, both in the fasting state and after the OGTT, were higher after GH treatment, but the ratio between amylin and insulin remained unchanged. CONCLUSIONS: GH-induced hyperinsulinemia is accompanied by proportionate elevations in amylin concentrations and a blunting of gut GLP-1 secretion. The mechanisms underlying the suppression of GLP-1 remain to be elucidated.


Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 122
Author(s):  
David Ramiro-Cortijo ◽  
Ángel Luis López de Pablo ◽  
Mᵃ Rosario López-Giménez ◽  
Camilia R. Martin ◽  
Joanne Brown ◽  
...  

After birth, preterm infants are deficient in arachidonic acid (ARA), docosahexaenoic acid (DHA), and antioxidants, increasing their risk of oxidative stress-related pathologies. The principal aim was to evaluate if supplementation with long-chain polyunsaturated fatty acids (LCPUFAs) improves antioxidant defenses. In total, 21 preterm infants were supplemented with ARA and DHA in a 2:1 ratio (ARA:DHA-S) or with medium-chain triglycerides (MCT-S). Plasma n-3 and n-6 LCPUFAs were measured at birth, postnatal day 28, and 36 weeks of postmenstrual age (36 WPA) by gas chromatography–mass spectroscopy. Plasma antioxidants (glutathione (GSH), catalase, and thiols) and oxidative damage biomarkers (malondialdehyde (MDA), carbonyls) were analyzed at the same time points by spectrophotometry, and scores of antioxidant status (Antiox-S) and oxidative damage (Proxy-S) were calculated. At 36 WPA, linoleic acid (LA) and dihomo-γ-linolenic acid (DGLA) were decreased in ARA:DHA-S compared to the MCT-S group (LA: ARA:DHA-S = 18.54 ± 1.68, MCT-S = 22.80 ± 1.41; p = 0.018; DGLA: ARA:DHA-S = 1.68 ± 0.38, MCT-S = 2.32 ± 0.58; p = 0.018). Furthermore, α-linolenic acid (ALA) was increased in ARA:DHA-S (ARA:DHA-S = 0.52 ± 0.33, MCT-S = 0.22 ± 0.10; p = 0.018). Additionally, LA:DHA ratio was decreased in the ARA:DHA-S compared to control group (ARA:DHA-S = 6.26 ± 2.35, MCT-S = 8.21 ± 2.65; p = 0.045). By the end of supplementation (36 WPA), catalase, thiol groups, and Antiox-S were significantly higher in neonates receiving ARA:DHA-S compared to those receiving MCT-S, with no differences in oxidative stress biomarkers. In conclusion, ARA:DHA supplementation in preterm neonates resulted in an overall improvement in antioxidant to oxidant balance and a decrease in early fatty acid precursors of the n-6 relative to the n-3 pathway. These effects may reduce oxidative stress and inflammation.


2003 ◽  
Vol 182 (2) ◽  
pp. 141-147 ◽  
Author(s):  
Laksami N. Yatham ◽  
Fred Grossman ◽  
Ilse Augustyns ◽  
Eduard Vieta ◽  
Arun Ravindran

BackgroundFew double-blind trials have examined the efficacy of a combination of a mood stabiliser and an atypical antipsychotic in acute mania.AimsTo determine the efficacy of risperidone in combination with a mood stabiliser in acute mania.MethodPatients taking a mood stabiliser were randomised to 3 weeks' treatment with risperidone (n=75) or placebo (n=76).ResultsYoung Mania Rating Scale (YMRS) scores improved rapidly with significantly greater reductions at week 1 in the risperidone group compared with the placebo group. At end-point YMRS scores decreased by 14.5 and 10.3 points in the risperidone and placebo groups, respectively. Significant improvements v. placebo (P < 0.05) were noted in the risperidone group on several other clinically meaningful measures. Additionally, a post hoc analysis excluding carbamazepine-treated patients (plasma concentrations of risperidone active moiety were 40% lower in this group) revealed significantly greater reductions (P=0.047) in YMRS scores in the risperidone group than in the placebo group. Incidence of adverse events was similar in both groups.ConclusionsRisperidone is superior to placebo when used in combination with lithium or divalproex in acute mania.


Neonatology ◽  
2021 ◽  
Vol 118 (1) ◽  
pp. 106-113
Author(s):  
Aline G.J. Engbers ◽  
Swantje Völler ◽  
Christian F. Poets ◽  
Catherijne A.J. Knibbe ◽  
Irwin K.M. Reiss ◽  
...  

Background: Apnea of prematurity can persist despite caffeine therapy in preterm infants. Doxapram may additionally support breathing. Although multiple small studies have reported the efficacy of doxapram, the structural co-treatment with caffeine impedes to ascribe the efficacy to doxapram itself or to a pharmacokinetic (PK) interaction where doxapram increases the exposure to caffeine. We examined whether there is a PK drug-drug interaction between doxapram and caffeine by developing a PK model for caffeine including infants with and without doxapram treatment. Methods: In preterm neonates receiving caffeine, we determined caffeine plasma concentrations before, during, and directly after doxapram co-treatment and used these to develop a population PK model in NONMEM 7.3. Patient characteristics and concomitant doxapram administration were tested as covariates. Results: 166 plasma samples were collected from 39 preterm neonates receiving caffeine (median gestational age 25.6 [range 24.0–28.0] weeks) of which 65 samples were taken during co-treatment with doxapram (39%, from 32/39 infants). Clearance of caffeine was 9.99 mL/h for a typical preterm neonate with a birth weight of 0.8 kg and 23 days postnatal age and increased with birth weight and postnatal age, resulting in a 4-fold increase in clearance during the first month of life. No PK interaction between caffeine and doxapram was identified. Discussion: Caffeine clearance is not affected by concomitant doxapram therapy but shows a rapid maturation with postnatal age. As current guidelines do not adjust the caffeine dose with postnatal age, decreased exposure to caffeine might partly explain the need for doxapram therapy after the first week of life.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Alicia Jiménez-Delgado ◽  
Genaro Gabriel Ortiz ◽  
Daniela L. Delgado-Lara ◽  
Hector Alberto González-Usigli ◽  
Luis Javier González-Ortiz ◽  
...  

Mitochondrial dysfunction and oxidative stress are extensively linked to Parkinson’s disease (PD) pathogenesis. Melatonin is a pleiotropic molecule with antioxidant and neuroprotective effects. The aim of this study was to evaluate the effect of melatonin on oxidative stress markers, mitochondrial complex 1 activity, and mitochondrial respiratory control ratio in patients with PD. A double-blind, cross-over, placebo-controlled randomized clinical trial study was conducted in 26 patients who received either 25 mg of melatonin or placebo at noon and 30 min before bedtime for three months. At the end of the trial, in patients who received melatonin, we detected a significant diminution of lipoperoxides, nitric oxide metabolites, and carbonyl groups in plasma samples from PD patients compared with the placebo group. Conversely, catalase activity was increased significantly in comparison with the placebo group. Compared with the placebo group, the melatonin group showed significant increases of mitochondrial complex 1 activity and respiratory control ratio. The fluidity of the membranes was similar in the melatonin group and the placebo group at baseline and after three months of treatment. In conclusion, melatonin administration was effective in reducing the levels of oxidative stress markers and restoring the rate of complex I activity and respiratory control ratio without modifying membrane fluidity. This suggests that melatonin could play a role in the treatment of PD.


2009 ◽  
Vol 2 (4) ◽  
pp. 247-254 ◽  
Author(s):  
Michael I. C. Kingsley ◽  
Daniel Cunningham ◽  
Laura Mason ◽  
Liam P. Kilduff ◽  
Jane McEneny

Many degenerative diseases are associated with increased oxidative stress. Creatine has the potential to act as an indirect and direct antioxidant; however, limited data exist to evaluate the antioxidant capabilities of creatine supplementation within in vivo human systems. This study aimed to investigate the effects of oral creatine supplementation on markers of oxidative stress and antioxidant defenses following exhaustive cycling exercise. Following preliminary testing and two additional familiarization sessions, 18 active males repeated two exhaustive incremental cycling trials (T1 and T2) separated by exactly 7 days. The subjects were assigned, in a double-blind manner, to receive either 20 g of creatine (Cr) or a placebo (P) for the 5 days preceding T2. Breath-by-breath respiratory data and heart rate were continually recorded throughout the exercise protocol and blood samples were obtained at rest (preexercise), at the end of exercise (postexercise), and the day following exercise (post24 h). Serum hypdroperoxide concentrations were elevated at postexercise by 17 ± 5% above preexercise values (p = 0.030). However, supplementation did not influence lipid peroxidation (serum hypdroperoxide concentrations), resistance of low density lipoprotein to oxidative stress (t1/2maxLDL oxidation) and plasma concentrations of non-enzymatic antioxidants (retinol, α-carotene, β-carotene, α-tocopherol, γ-tocopherol, lycopene and vitamin C). Heart rate and oxygen uptake responses to exercise were not affected by supplementation. These findings suggest that short-term creatine supplementation does not enhance non-enzymatic antioxidant defence or protect against lipid peroxidation induced by exhaustive cycling in healthy males.


2017 ◽  
Vol 45 (8) ◽  
Author(s):  
Peymaneh Alizadeh Taheri ◽  
Negar Sajjadian ◽  
Marzieh Asgharyan Fargi ◽  
Mamak Shariat

AbstractObjective:Breast feeding alone does not provide adequate nutrition for growth in preterm infants; therefore, fortifiers are added when over 70–80 cc/kg/day of breast milk is tolerated. As there are few studies comparing early and late breast milk fortification, the following study was conducted.Study design:This double-blind clinical trial was performed on 80 preterm infants (gestational age of 28–34 weeks, birth weight <2 kg). The newborns were randomly divided into two groups to receive either early or late fortification. The primary and secondary outcomes were the difference in growth indices and complications (including feeding intolerance, necrotizing enterocolitis (NEC), and septicemia) between the two groups, respectively.Results:Both groups showed increases in growth indices; however, there was no statistically significant difference in increments of growth indices and complications between the two groups.Conclusion:Our findings suggest that early fortification from the first feeding in neonates with exclusive breast feeding did not improve growth in the first 4 weeks in preterm neonates in comparison with late fortification; so early fortification may not be cost effective.


2016 ◽  
Vol 44 (5) ◽  
Author(s):  
Carla Balcells ◽  
Francesc Botet ◽  
Sònia Gayete ◽  
M Ángeles Marcos ◽  
Izaskun Dorronsoro ◽  
...  

AbstractTo determine the epidemiology of congenital and acquired cytomegalovirus (CMV) infections in preterm infants and to analyze the efficacy of breast milk freezing in decreasing the vertical transmission rate of CMV.During 2013 and 2014, preterm newborns who weighed ≤1500 g and were admitted to 22 Spanish neonatal units were included and screened for CMV infection according to the Spanish Neonatology Society recommendations. Each hospital treated the breast milk according to its own protocols.Among the 1236 preterm neonates included, 10 had a congenital infection (0.8%) and 49 had an acquired infection (4.0%) (82% demonstrated positive PCR-CMV in breast milk). The neonates who received only frozen milk presented less frequently with acquired infection (1.2%) than those fed fresh milk (5.5%) (RR=0.22; 95% CI 0.05–0.90; P=0.017). The newborns who received bank milk followed by frozen or fresh breast milk more frequently had an acquired infection (2.1% or 2.2%, respectively) than those fed only frozen breast milk.The incidence of congenital CMV infection in our sample is low, as described in the literature. To reduce acquired CMV infection, freezing breast milk might be an advisable procedure for preterm neonates born from seropositive mothers, either from the beginning of lactation or after a period of bank milk administration.


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