title: Melatonin decreases the expression of inflammation and apoptosis markers in the lung of a senescence-accelerated mice model.
abstract: Aging is associated with an increase in oxidative stress and inflammation. The aging lung is particularly affected since it is continuously exposed to environmental oxidants while antioxidant machinery weakens with age. Melatonin, a free radical scavenger, counteracts inflammation and apoptosis in healthy cells from several tissues. Its effects on the aging lung are, however, not yet fully understood. This study aimed to investigate the effect of chronic administration of melatonin on the expression of inflammation markers (TNF-α, IL-1β, NFκB2, HO-1) and apoptosis parameters (BAD, BAX, AIF) in the lung tissue of male senescence-accelerated prone mice (SAMP8). In addition, RNA oxidative damage, as the formation of 8-hydroxyguanosine (8-OHG), was also evaluated. Young and old animals, aged 2 and 10 months respectively, were divided into 4 groups: untreated young, untreated old, old mice treated with 1mg/kg/day melatonin, and old animals treated with 10mg/kg/day melatonin. Untreated young and old male senescence accelerated resistant mice (SAMR1) were used as controls. After 30 days of treatment, animals were sacrificed. Lungs were collected and immediately frozen in liquid nitrogen. mRNA and protein expressions were measured by RT-PCR and Western blotting, respectively. Levels of 8-OHG were quantified by ELISA. Mean values were analyzed using ANOVA. Old nontreated SAMP8 animals showed increased (p<0.05) mRNA and protein levels of TNF-α, IL-1β, NFκB2, and HO-1 compared to young mice and SAMR1 mice. Melatonin treatment with either dose reversed the aging-derived inflammation (p<0.05). BAD, BAX and AIF expressions also rose with aging, the effect being counteracted with melatonin (p<0.05). Aging also caused a significant elevation (p<0.05) in SAMP8 8-OHG values. This increase was not observed in animals treated with melatonin (p<0.05). In conclusion, melatonin treatment was able to modulate the inflammatory and apoptosis status of the aging lungs, exerting a protective effect on age-induced damage.
authors.affiliation: Department of Biochemistry and Molecular Biology III, School of Medicine, Complutense University of Madrid, Avda. Complutense s/n, 28040 Madrid, Spain. Electronic address: angela-puig91@gmail.com.
authors.forename: Ángela
authors.initials: Á
authors.lastname: Puig
authors.affiliation: Department of Biochemistry and Molecular Biology III, School of Medicine, Complutense University of Madrid, Avda. Complutense s/n, 28040 Madrid, Spain. Electronic address: lisa_rancan@hotmail.com.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rancan
authors.affiliation: Department of Physiology, School of Medicine, Complutense University of Madrid, Avda. Complutense s/n, 28040 Madrid, Spain. Electronic address: sergiodamianparedes@med.ucm.es.
authors.forename: Sergio D
authors.initials: SD
authors.lastname: Paredes
authors.affiliation: Department of Biochemistry and Molecular Biology III, School of Medicine, Complutense University of Madrid, Avda. Complutense s/n, 28040 Madrid, Spain. Electronic address: adriancamu8@gmail.com.
authors.forename: Adrián
authors.initials: A
authors.lastname: Carrasco
authors.affiliation: University of Granada, Institute of Biotechnology, Center of Biomedical Investigation, Edificio Fray Luis de Granada C/ Ramón y Cajal, 4, 18003 Granada, Spain. Electronic address: gescames@ugr.es.
authors.forename: Germaine
authors.initials: G
authors.lastname: Escames
authors.affiliation: Department of Biochemistry and Molecular Biology III, School of Medicine, Complutense University of Madrid, Avda. Complutense s/n, 28040 Madrid, Spain. Electronic address: evaraami@ucm.es.
authors.forename: Elena
authors.initials: E
authors.lastname: Vara
authors.affiliation: Department of Physiology, School of Medicine, Complutense University of Madrid, Avda. Complutense s/n, 28040 Madrid, Spain. Electronic address: guerres@med.es.
authors.forename: Jesús A F
authors.initials: JA
authors.lastname: Tresguerres
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019588:Aging, Premature / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008817:Mice, Mutant Strains; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D008550:Melatonin
keywords: Aging; Apoptosis; Inflammation; Lung; Melatonin; Oxidative stress