title: Effect of melatonin supplementation on plasma lipid hydroperoxides, homocysteine concentration and chronic fatigue syndrome in multiple sclerosis patients treated with interferons-beta and mitoxantrone.
abstract: Multiple sclerosis (MS) prevalence is higher in geographic regions with less sunlight exposure. Melatonin participates in the effects of sunlight in healthy individuals and could play a role in MS pathophysiology. Melatonin crosses the blood-brain barrier and exerts antioxidative, immunomodulatory, and anti-inflammatory effects. Chronic fatigue syndrome concerns 80 - 90% MS patients. The pathophysiology of chronic fatigue syndrome is unknown, however activation of immune, inflammatory, oxidative and nitrosative stress mechanisms and plasma lipid peroxide elevation was reported. Homocysteine increases plasma lipid hydroperoxides levels. The aim was to determine the effect of melatonin supplementation on chronic fatigue syndrome in MS patients and evaluate plasma lipid hydroxyperoxides (LHP) and homocysteine concentrations as a potential biochemical fatigue biomarkers. Into a case-control prospective study 102 MS patients divided according receiving immunomodifying MS treatment into groups: RRMS-pretreated, RRMS-INF-beta, SP/PPMS-mitoxantrone, RRMS-relapse were enrolled. Patients were supplemented with melatonin over 90 days. Plasma LHP, homocysteine concentration, brain MRI and fatigue score were examined. Results show that LHP concentrations were significantly higher in all studied MS groups vs.
  
  
  METHODS
  In all MS patient groups melatonin application resulted in significant decrease in plasma LHP concentrations. Plasma homocysteine concentration was similar in healthy people, RRMS-pretreated, RRMS-INF-beta and SP/PP-MS-mitoxantrone groups. However, in the RRMS-relapse group plasma levels of homocysteine were significantly higher compared to the RRMS-pretreated group. There were no significant differences in plasma homocysteine concentration in the studied groups before and after melatonin application. The fatigue score was significantly lower in RRMS pretreated group compared to RRMS-INF-beta and SP/PP MS-mitoxantrone treated patients. Plasma lipid hydroxyperoxides could be potential biochemical chronic fatigue syndrome biomarker in MS patients and homocysteine could be a potential marker of acute phase of MS. Melatonin exerts beneficial effects in MS patients based on its' proved antioxidative properties.
authors.affiliation: Department of Neurology in Zabrze, Medical University of Silesia, Zabrze, Poland. m.adamczyk.sowa@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Adamczyk-Sowa
authors.affiliation: ENT Department in Zabrze, Medical University of Silesia, Zabrze, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Sowa
authors.affiliation: Department of Physiology in Zabrze, Medical University of Silesia, Zabrze, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Adamczyk
authors.affiliation: Department of Neurology in Zabrze, Medical University of Silesia, Zabrze, Poland.
authors.forename: N
authors.initials: N
authors.lastname: Niedziela
authors.affiliation: Department of Anaesthesiology and Intensive Therapy, Medical University of Silesia, Katowice, Poland.
authors.forename: H
authors.initials: H
authors.lastname: Misiolek
authors.affiliation: Department of Neurology in Zabrze, Medical University of Silesia, Zabrze, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Owczarek
authors.affiliation: Department of Physiology in Zabrze, Medical University of Silesia, Zabrze, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Zwirska-Korczala
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging; D019587:Dietary Supplements; D015673:Fatigue Syndrome, Chronic / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use; D008054:Lipid Peroxides / Q000097:blood*; D008279:Magnetic Resonance Imaging; D008297:Male; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D008942:Mitoxantrone / Q000494:pharmacology / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000975:Antioxidants; D007155:Immunologic Factors; D008054:Lipid Peroxides; D006710:Homocysteine; D016899:Interferon-beta; D008942:Mitoxantrone; D008550:Melatonin