Mistraletti Giovanni, Paroni Rita, Umbrello Michele, D'Amato Lara, Sabbatini Giovanni, Taverna Martina, Formenti Paolo, Finati Elena, Favero Gaia, Bonomini Francesca, Rezzani Rita, Reiter Russel J, Iapichino Gaetano
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20142 Milano, Italy.
Department of Anesthesia and Intensive Care, ASST Santi Paolo e Carlo, San Paolo University Hospital, 20142 Milano, Italy.
Int J Mol Sci. 2017 Apr 3;18(4):759. doi: 10.3390/ijms18040759.
In this study, the aim was to test the biochemical effects of melatonin supplementation in Intensive Care Unit (ICU) patients, since their blood levels are decreased. Sixty-four patients were enrolled in the study. From the evening of the 3rd ICU day, patients were randomized to receive oral melatonin (3 mg, group M) or placebo (group P) twice daily, at 20:00 and 24:00, until discharged. Blood was taken (at 00:00 and 14:00), on the 3rd ICU day to assess basal nocturnal melatonin values, and then during the treatment period on the 4th and 8th ICU days. Melatonin, total antioxidant capacity, and oxidative stress were evaluated in serum. Melatonin circadian rhythm before treatment was similar in the two groups, with a partial preservation of the cycle. Four hours from the 1st administration (4th ICU day, 00:00), melatonin levels increased to 2514 (982.3; 7148) pg·mL in group M vs. 20.3 (14.7; 62.3) pg·mL in group P ( < 0.001). After five treatment days (8th ICU day), melatonin absorption showed a repetitive trend in group M, while in group P nocturnal secretion (00:00) was impaired: 20 (11.5; 34.5) pg·mL vs. 33.8 (25.0; 62.2) on the 3rd day ( = 0.029). Immediately from the beginning of treatment, the total antioxidant capacity was significantly higher in melatonin treated subjects at 00:00; a significant correlation was found between total antioxidant capacity and blood melatonin values (ρ = 0.328; < 0.001). The proposed enteral administration protocol was adequate, even in the early phase, to enhance melatonin blood levels and to protect the patients from oxidative stress. The antioxidant effect of melatonin could play a meaningful role in the care and well-being of these patients.
在本研究中，由于重症监护病房（ICU）患者的血液褪黑素水平会降低，因此目的是测试补充褪黑素对他们的生化影响。64名患者参与了该研究。从入住ICU的第3天晚上开始，患者被随机分为两组，每天两次（20:00和24:00）口服褪黑素（3毫克，M组）或安慰剂（P组），直至出院。在入住ICU的第3天（00:00和14:00）采集血液，以评估基础夜间褪黑素值，然后在入住ICU的第4天和第8天的治疗期间采集血液。对血清中的褪黑素、总抗氧化能力和氧化应激进行评估。两组治疗前的褪黑素昼夜节律相似，周期有部分保留。首次给药后4小时（入住ICU的第4天，00:00），M组的褪黑素水平升至2514（982.3；7148）pg·mL，而P组为20.3（14.7；62.3）pg·mL（P<0.001）。治疗5天后（入住ICU的第8天），M组的褪黑素吸收呈现重复趋势，而P组的夜间分泌（00:00）受损：第8天为20（11.5；34.5）pg·mL，第3天为33.8（25.0；62.2）pg·mL（P = 0.029）。从治疗开始即刻，00:00时褪黑素治疗组受试者的总抗氧化能力显著更高；总抗氧化能力与血液褪黑素值之间存在显著相关性（ρ = 0.328；P<0.001）。所建议的肠内给药方案即使在早期阶段也足以提高血液褪黑素水平，并保护患者免受氧化应激影响。褪黑素的抗氧化作用可能对这些患者的护理和健康发挥重要作用。
