title: Melatonin Pharmacological Blood Levels Increase Total Antioxidant Capacity in Critically Ill Patients.
abstract: 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-1in group M vs. 20.3 (14.7; 62.3) pg·mL-1in group P (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-1vs. 33.8 (25.0; 62.2) on the 3rd day (p= 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;p< 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.
authors.affiliation: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20142 Milano, Italy. giovanni.mistraletti@unimi.it.|Department of Anesthesia and Intensive Care, ASST Santi Paolo e Carlo, San Paolo University Hospital, 20142 Milano, Italy. giovanni.mistraletti@unimi.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mistraletti
authors.affiliation: Department of Health Science, Università degli Studi di Milano, 20142 Milano, Italy. rita.paroni@unimi.it.
authors.forename: Rita
authors.initials: R
authors.lastname: Paroni
authors.affiliation: Department of Anesthesia and Intensive Care, ASST Santi Paolo e Carlo, San Paolo University Hospital, 20142 Milano, Italy. michele.umbrello@asst-santipaolocarlo.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Umbrello
authors.affiliation: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20142 Milano, Italy. lara.damato@unimi.it.
authors.forename: Lara
authors.initials: L
authors.lastname: D'Amato
authors.affiliation: Department of Anesthesia and Intensive Care, ASST Santi Paolo e Carlo, San Paolo University Hospital, 20142 Milano, Italy. giovanni.sabbatini1@gmail.com.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sabbatini
authors.affiliation: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20142 Milano, Italy. martinatav@libero.it.
authors.forename: Martina
authors.initials: M
authors.lastname: Taverna
authors.affiliation: Department of Anesthesia and Intensive Care, ASST Santi Paolo e Carlo, San Paolo University Hospital, 20142 Milano, Italy. formenti.paolo@faswebnet.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Formenti
authors.affiliation: Department of Health Science, Università degli Studi di Milano, 20142 Milano, Italy. ele.finati@gmail.com.
authors.forename: Elena
authors.initials: E
authors.lastname: Finati
authors.affiliation: Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy. gaia.favero@unibs.it.
authors.forename: Gaia
authors.initials: G
authors.lastname: Favero
authors.affiliation: Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy. francesca.bonomini@unibs.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bonomini
authors.affiliation: Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy. rita.rezzani@unibs.it.
authors.forename: Rita
authors.initials: R
authors.lastname: Rezzani
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Centre, San Antonio, TX 78229-3900, USA. reiter@uthscsa.edu.
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
authors.affiliation: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20142 Milano, Italy. g.iapichino@unimi.it.|Department of Anesthesia and Intensive Care, ASST Santi Paolo e Carlo, San Paolo University Hospital, 20142 Milano, Italy. g.iapichino@unimi.it.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Iapichino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D002940:Circadian Rhythm; D016638:Critical Illness; D045304:Cytochromes c / Q000378:metabolism; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D018613:Microscopy, Confocal; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000975:Antioxidants; D045304:Cytochromes c; D052247:Nitric Oxide Synthase Type II; D008550:Melatonin
keywords: antioxidants; critical illness; dietary supplements; melatonin; oxidative stress