title: Evidence of oxidative injury during aging of the liver in a mouse model.
abstract: The aim of the present study was to determine whether oxidative stress contributes to aging of the liver in a mouse model. Liver was obtained from young (3-5 months old) and aged (18-24 months old) mice. No age-induced gross changes in liver morphology were detected by light microscopy. Apoptosis was measured using the fragment end labeling of DNA for the immunohistochemical identification of the apoptotic nuclei. The total apoptotic cells represented 1% of the total cells in livers of young mice and 8% in those of aged mice. Among the total apoptotic cells in livers of aged animals, 15% were hepatocytes, 40% sinusoidal endothelial cells, and 45% bile duct cells. Hepatic lipid peroxidation, expressed as malonaldehyde levels, protein oxidation, measured by protein carbonyl content, and DNA oxidation, measured as 8-hydroxy-2'-deoxyguanosine (oxo(8)dG), were significantly increased in the livers of aged animals as compared to younger mice. The apoptotic cells presented elevated levels of oxidized DNA, detected by immunohistochemistry using an antibody directed against oxo(8)dG in serial sections. These results suggest that livers of aged animals presents evidence of increased oxidative injury and apoptosis. Because the apoptotic cells in the aged livers are mostly bile duct cells and sinusoidal endothelial cells, the cells most sensitive to oxidative stress injury, it can be hypothesized that reactive oxygen species-induced apoptosis in these cells contributes to the aging of the liver.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Loyola University Chicago, Maywood, IL ; Immunology and Aging Program, Department of Cell Biology Neurobiology and Anatomy, Loyola University Chicago, Maywood, IL.
authors.forename: A
authors.initials: A
authors.lastname: Colantoni
authors.forename: R
authors.initials: R
authors.lastname: Idilman
authors.forename: N
authors.initials: N
authors.lastname: de Maria
authors.forename: L A
authors.initials: LA
authors.lastname: Duffner
authors.forename: D H
authors.initials: DH
authors.lastname: Van Thiel
authors.forename: P L
authors.initials: PL
authors.lastname: Witte
authors.forename: E J
authors.initials: EJ
authors.lastname: Kovacs