title: Melatonin is able to reduce the apoptotic liver changes induced by aging via inhibition of the intrinsic pathway of apoptosis.
abstract: We examined the effect of daily melatonin supplementation on liver apoptosis induced by aging in rats. Young (3-month-old) and aged (24-month-old) Wistar rats were supplemented daily with melatonin in their drinking water (20 mg/L) for 4 weeks. Aged rats showed increases in the liver concentration of thiobarbituric acid-reactive substances and in the oxidized/reduced glutathione ratio. These increases were accompanied by apoptotic ultrastructural alterations and increases in cytochrome c mitochondrial release, Bax to Bcl-2 relative expression, and activity of caspase-3. No significant changes were observed in Fas-ligand (Fas-L) expression and caspase-8 activity. Melatonin administration was able to abrogate changes detected in aged rats. Data suggest that liver apoptotic cell death is induced by reactive oxygen species, via the intrinsic signalling pathway, and that the antiapoptotic action provided by melatonin is related to its antioxidant effect, with reduction of cytochrome c release by the modulation of Bcl-2 and Bax genes.
authors.affiliation: Ciberehd and Institute of Biomedicine, Department of Biomedical Sciences, University of León, 24071-León, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Molpeceres
authors.forename: José L
authors.initials: JL
authors.lastname: Mauriz
authors.forename: María V
authors.initials: MV
authors.lastname: García-Mediavilla
authors.forename: Paquita
authors.initials: P
authors.lastname: González
authors.forename: Juan P
authors.initials: JP
authors.lastname: Barrio
authors.forename: Javier
authors.initials: J
authors.lastname: González-Gallego
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000648:ultrastructure*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013858:Thiobarbiturates / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D013858:Thiobarbiturates; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8; D005978:Glutathione; D008550:Melatonin; C029684:thiobarbituric acid