Melatonin reduces oxidative stress in surgical neonates

BACKGROUND/PURPOSE: Cytokines are inflammatory mediators found in the circulation after surgery. Newborns have less protection against oxidation and are very susceptible to free radical oxidative damage. Melatonin has been reported recently to reduce oxidative stress in neonates with sepsis, asphyxia, and respiratory distress. The aim of this study has been to determine if melatonin would lower interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-alpha) and nitrite/nitrate (NOx) levels and modify serum inflammation parameters, improving the clinical course of surgical neonates. METHODS: Ten newborns (group 1), 5 with surgical malformations and respiratory distress (group 1a) and 5 with isolated abdominal surgical malformations (group 1b) received a total of 10 doses of melatonin (10 mg/kg) at defined times interval for 72 hours. The treatment was started within 3 hours after the end of surgery. Ten surgical neonates (group 2), did not receive melatonin. Twenty healthy neonates (group 3) served as control. Blood samples were collected at the end of operation; before treatment with the antioxidant; and 24 hours 72 hours, and 7 days after start of treatment with melatonin or placebo, respectively. RESULTS: Postoperative value of cytokines and NOx levels of groups 1 and 2 were significantly higher than group 3. Compared with group 1b, group 2 displayed significantly higher cytokines and NOx levels at 24 hours, 72 hours, and at 7 days. In group 1a the immediate postoperative values of cytokines were significantly higher than group 1b and group 2, but a significant improvement was observed after administration of melatonin with significantly lower levels of IL-6 and IL-8 with respect to group 2. An improvement of clinical outcome was observed by progressive reduction of clinical parameters of inflammation. CONCLUSIONS: Melatonin reduces cytokines and NOx levels showing potent antioxidant properties with improvement in clinical outcome. Further studies are warranted to define, on larger numbers, the role of melatonin in surgical patients.