Evidence of oxidative injury during aging of the liver in a mouse model

被引:13
作者
Colantoni A. [1 ]
Idilman R. [1 ]
De Maria N. [1 ]
Duffner L.A. [1 ]
Van Thiel D.H. [1 ]
Witte P.L. [1 ]
Kovacs E.J. [1 ]
机构
[1] Division of Gastroenterology, Loyola University Medical Center, Maywood, IL 60153
关键词
Protein Carbonyl; Oxidative Injury; Young Mouse; Aged Animal; Carbonyl Content;
D O I
10.1007/s11357-001-0007-3
中图分类号
学科分类号
摘要
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.
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页码:51 / 57
页数:6
相关论文
共 36 条
[1]  
O'Mahony M.S., Schmucker D.I., Liver disease in the elderly, Sem. Gastrointest. Dis., 5, pp. 197-206, (1994)
[2]  
Monette J., Gurwitz J.H., Avorn J., Epidemiology of adverse drug events in the nursing home setting, Drugs Aging, 7, pp. 203-211, (1995)
[3]  
LeCouteur D.G., McLean A.J., The aging liver, Clin. Pharmacokinet., 34, pp. 359-373, (1998)
[4]  
Maher J.J., Friedman S.L., Parenchymal and nonparenchymal cell interactions in the liver, Sem. Liver Dis., 13, pp. 13-20, (1993)
[5]  
Stadtman E.R., Protein oxidation and aging, Science, 257, pp. 1220-1224, (1992)
[6]  
Higami Y., Shimokawa I., Apoptosis in the aging process, Cell Tissue Res., 301, pp. 125-132, (2000)
[7]  
Colantoni A., De Maria N., Caraceni P., Bernardi M., Van Thiel D.H., Gender influences cold preservation-reoxygenation injury in the liver, Transplant. Proc., 31, pp. 1052-1053, (1999)
[8]  
Colantoni A., La Paglia N., De Maria N., Emanuele M.A., Emanuele N.V., Idilman R., Harig J., Van Thiel D.H., Relationship between sex hormonal status and oxidative liver injury in male and female rats fed alcohol, Alcohol. Clin. Exp. Res., 24, pp. 1467-1473, (2000)
[9]  
Colantoni A., De Maria N., Caraceni P., Bernardi M., Floyd R.A., Van Thiel D.H., Prevention of reoxygenation injury by sodium salicylate in isolated-perfused rat liver, Free Rad. Biol. Med., 25, pp. 87-94, (1998)
[10]  
Burt A.D., LeBail B., Balabaud C., Bioulac-Sage P., Morphologic investigation of sinusoidal cells, Sem. Liver Dis., 13, pp. 21-38, (1993)