title: Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients with Xeroderma Pigmentosum Group A.
abstract: Xeroderma pigmentosum group A (XPA) is a genetic disorder in DNA nucleotide excision repair (NER) with severe neurological disorders, in which oxidative stress and disturbed melatonin metabolism may be involved. Herein we confirmed the diurnal variation of melatonin metabolites, oxidative stress markers, and antioxidant power in urine of patients with XPA and age-matched controls, using enzyme-linked immunosorbent assay (ELISA). The peak of 6-sulfatoxymelatonin, a metabolite of melatonin, was seen at 6:00 in both the XPA patients and controls, though the peak value is lower, specifically in the younger age group of XPA patients. The older XPA patients demonstrated an increase in the urinary levels of 8-hydroxy-2'-deoxyguanosine and hexanoyl-lysine, a marker of oxidative DNA damage and lipid peroxidation, having a robust peak at 6:00 and 18:00, respectively. In addition, the urinary level of total antioxidant power was decreased in the older XPA patients. Recently, it is speculated that oxidative stress and antioxidant properties may have a diurnal variation, and the circadian rhythm is likely to influence the NER itself. We believe that the administration of melatonin has the possibility of ameliorating the augmented oxidative stress in neurodegeneration, especially in the older XPA patients, modulating the melatonin metabolism and the circadian rhythm.
authors.affiliation: Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan; Department of Pediatrics, Tokyo-Kita Medical Center, Tokyo 171-0053, Japan.
authors.forename: Rie
authors.identifier: 0000-0002-1040-4936
authors.initials: R
authors.lastname: Miyata
authors.affiliation: Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan; Department of Pediatrics, Tokyo Metropolitan Fuchu Medical Center for the Disabled, Tokyo 183-8553, Japan.
authors.forename: Naoyuki
authors.identifier: 0000-0003-0545-1831
authors.initials: N
authors.lastname: Tanuma
authors.affiliation: Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakuma
authors.affiliation: Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
authors.forename: Masaharu
authors.identifier: 0000-0002-5545-0741
authors.initials: M
authors.lastname: Hayashi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism* / Q000652:urine; D002648:Child; D002940:Circadian Rhythm; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D008239:Lysine / Q000652:urine; D008550:Melatonin / Q000378:metabolism* / Q000652:urine; D018384:Oxidative Stress; D014983:Xeroderma Pigmentosum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology* / Q000652:urine; D055815:Young Adult
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D008550:Melatonin; D008239:Lysine