الفهرس 
Melatonin
Protective role of melatonin in neonatal diseasesOnly 14 pages are availabe for public view
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Abstract
Despite advances in antimicrobial therapy and supportive cares, neonatal sepsis is a major cause of death worldwide. In developing countries, many of the more than 14 million deaths of children under five years of age occur during the neonatal period, with sepsis accounting for up to 70% of total mortality for this age group.
Newborns and especially preterm infants are probably more prone to oxidative stress than other children and young adults. There are some special reasons for this. These infants very often are exposed to high oxygen concentrations, have infections or inflammation, have reduced antioxidant defense, and have free iron which enhances the Fenton reaction leading to production of highly toxic hydroxyl radicals.
Oxygen-derived metabolites, collectively termed reactive oxygen species, are normally produced in aerobic organisms. Oxidative stress is defined as an imbalance between prooxidant and antioxidant forces leading to an overall prooxidant insult.
Melatonin is an endogenously produced indolamine principally synthesized in the pineal gland from the neurotransmitter serotonin.Prematurity itself does not hasten the maturation of the neurological network controlling melatonin secretion, Therefore; in premature neonates the melatonin deficiency is more prolonged.Melatonin acts as a potent endogenous antioxidant by scavenging free radicals and upregulating antioxidant pathways. The activity and expression of antioxidant enzymes such as superoxide dismutase, glutathione catalase, glutathione peroxidase, and glutathione reductase have been shown to be increased by melatonin, supporting its indirect antioxidant action. Further evidence of the antioxidant effect of melatonin is provided by its ability to reduce lipid peroxidation involved in the pathogenesis of many diseases.
The use of melatonin treatment during the late fetal and early neonatal period might result in a wide range of health benefits, improve quality of life and may help limit complications during the critical periods prior to and shortly after delivery. In light of its properties melatonin has been used as an adjuvant in the treatment of free radical disease in the newborn, and several evidences suggest a role for melatonin in perinatal disorders, including asphyxia, RDS, surgical processes, and sepsis.
Malondialdehyde (MDA) is an end-product of the radical-initiated oxidative decomposition of polyunsaturated fatty acids and it is considered the principal and most studied product of polyunsaturated fatty acid peroxidation and frequently used as a biomarker of oxidative stress.
There is overwhelming evidence that oxidative stress plays a significant role in the pathogenesis of sepsis-associated multiple organ failure.The lipid peroxidation, as a result of ROS production, play a significant role in pathogenesis of multiple organ failure and septic shock associated with neonatal sepsis which contribute to high morbidity and mortality.
This work was designed to assess the efficacy of melatonin as an adjuvant in the treatment of free radical disease in septic preterms receiving melatonin compared to those on conventional treatment through measuring the level of MDA as a marker of oxidative stress and by comparing other clinical and laboratory parameters of sepsis in both groups.
The study included 36 males and 19 females with gestational ages ranged between 26 and 36 weeks, 10 delivered vaginally and 45 delivered by caesarean section, Forty septic preterm infants were included and were subsequently randomized by permuted block randomization according to sequence of enrollment into:
Melatonin treated (MT): neonates with odd numbers received melatonin.
Conventionally treated (CT): neonates with even numbers didn’t receive the medicine.
Melatonin Medication:
Melatonin was given at a total dose of 20 mg dissolved in 4 ml of distilled water via enteral route in two doses of 10 mg each(2 ml), with a 1-hour interval.Non Sepsis group: 15 healthy neonates, in whom sepsis was ruled-out on the basis of absence of any clinical or laboratory evidence suggestive of infection
Blood samples were collected from melatonin treated group at enrollment and after 6 and 72 hours of melatonin administration while samples were collected from conventionally treated group at enrollment and after 72 hours of admission.
Blood samples were collected from 15 healthy preterm infants at day 1 for MDA assay to serve as a control group.
Plasma levels of MDA in the samples were detected by Colorimetric method using Lipid Peroxide (Malondialdehyde) Assay Kit.
Both studied sepsis sub-groups (MT group and CT group) showed no significant difference as regard demographic characteristics in terms of sex, gestational age, mode of delivery, birth weight and Apgar scores and were also comparable with healthy controls in some demographic characters in terms of sex, gestational age and mode of delivery, however healthy controls had lower birth weight and higher Apgar scores than both sepsis subgroups.
At time of enrollment in our study, the initial conditions were identical in both Melatonin treated and Conventionally treated septic preterms, they showed no significant difference in clinical signs of infections and Rodwell scores, they had same hemodynamic statuses in terms of mean arterial pressures and need for inotropic support, and they had the same oxygen requirements.Melatonin administration decreased the length of stay of septic preterms in NICU and reduced incidence of mortality in melatonin treated septic group(0%), compared to the other conventionally treated septic group(30%).
Our study showed no significant difference between both septic groups regarding all laboratory data at time of enrollment and we found that melatonin improved the clinical outcome of melatonin treated septic preterms through improving the sepsis related serum parameters after 72 h of melatonin administration as an adjuvant therapy to septic preterms in comparison to conventionally treated septic group.
Lipid peroxidation, as reflected by serum MDA levels, was significantly higher in both septic groups compared to the serum MDA levels in their corresponding healthy controls.
Before administration of melatonin, MT group had a statistically significant higher baseline MDA levels than CT group, so according to the significance of MDA as a marker of lipid peroxidation in septic neonates we can postulate that the free radical load and oxidative stresses were even much higher in the MT group than the CT group.
Baseline MDA levels were significantly elevated after 72 h in CT group, conversely a high statistically significant decrease in MDA levels among MT group after 6 and 72 h of melatonin administration, with statistically significant lower 137
MDA levels than CT group after 72 h. These changes are consistent with melatonin’s ability to reduce the peroxidative breakdown of lipids in cell membranes.
No correlation was found between MDA baseline levels and different data in both septic groups, in the terms of birth weight, Apgar scores, maternal age, length of stay in NICU, MAP and Laboratory investigations done on day 1 (TLC, ANC, Platelet Count, CRP level), however we found a positive correlation between MDA baseline level in MT group and gestational age.