Melatonin reduces oxidative stress in surgical neonates

Melatonin reduces oxidative stress in surgical neonates
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DOI:
10.1016/j.jpedsurg.2003.10.003
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发表时间:
2004-02-01
影响因子:
2.4
通讯作者:
Zuccarello, B
Zuccarello, B
中科院分区:
医学3区
文献类型:
--
作者:
Gitto, E;Romeo, C;Zuccarello, B

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背景/目的:细胞因子是术后循环中发现的炎性介质。新生儿对氧化的保护作用较弱,非常容易受到自由基氧化损伤。褪黑素最近被报道可以减轻患有败血症、窒息和呼吸窘迫的新生儿的氧化应激。本研究旨在探讨褪黑素是否能降低IL-6、IL-8、肿瘤坏死因子α(TNF-α)和亚硝酸盐/硝酸盐(NOx)水平,改善新生儿炎症指标,改善新生儿的临床病程。方法:10例新生儿(第1组),5例合并呼吸窘迫的新生儿(1a组)和5例单纯腹部外科畸形的新生儿(1b组)分别给予褪黑素10 mg/kg,每次10 mg/kg,每次间隔72h。在手术结束后3小时内开始治疗。手术新生儿10例(第2组),未接受褪黑素治疗。健康新生儿20例(第3组)作为对照。分别于手术结束、抗氧化剂治疗前、褪黑素或安慰剂治疗后24小时、72小时和7天采血。结果:1、2组术后细胞因子和NOx水平均显著高于3组,2组在24小时、72小时和7天显著高于1b组。1a组术后即刻细胞因子水平明显高于1b组和2b组,应用褪黑激素后IL-6和IL-8水平明显低于2b组,IL-6和IL-8水平明显低于2b组。结论:褪黑素降低了细胞因子和NOx水平,改善了临床预后。有必要进行进一步的研究,在更多的病例中确定褪黑激素在外科患者中的作用。
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 la 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.