Age-Associated Increase in Ferritin Content of Male Rat Liver: Implication for Diquat-Mediated Oxidative Injury

Our previous studies in rat hepatocytes demonstrated an age-dependent increase in sensitivity to diquat-induced cytotoxicity, possibly as a result of increased iron availability. The present study was conducted to determine whether quantitative or qualitative changes in hepatic ferritin occur as a c...

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Bibliographic Details
Published in:Archives of biochemistry and biophysics 1997-08, Vol.344 (1), p.85-93
Main Authors: Rikans, Lora E., Ardinska, Vita, Hornbrook, K.Roger
Format: Article
Language:English
Subjects:
aging
Aging - metabolism
Animals
Deferoxamine - pharmacology
DICUAT
DIQUAT
Diquat - toxicity
ferritin
Ferritins - chemistry
Ferritins - metabolism
FOIE
HIGADO
iron
Iron - metabolism
Kinetics
Lipid Peroxidation - drug effects
Liver - drug effects
Liver - metabolism
Male
Microsomes, Liver - drug effects
Microsomes, Liver - metabolism
NADH Dehydrogenase - metabolism
NADP - metabolism
Organ Size
Oxidative Stress
Protein Conformation
Proteins - metabolism
RAT
rat liver
RATA
Rats
Rats, Inbred F344
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Summary:Our previous studies in rat hepatocytes demonstrated an age-dependent increase in sensitivity to diquat-induced cytotoxicity, possibly as a result of increased iron availability. The present study was conducted to determine whether quantitative or qualitative changes in hepatic ferritin occur as a consequence of aging and whether diquat-mediated oxidation is intensified by elevated ferritin concentrations. Hepatic ferritins were isolated from male Fischer 344 rats ages 5, 15, and 25 months. Age-associated increases were observed in amounts of ferritin protein and ferritin iron per gram of liver, but there were no differences in proportions of H to L subunits or in rates of diquat-mediated iron release. The consequences of a threefold increase in ferritin content for diquat-mediated lipid peroxidation and protein carbonyl formation were examined in microsomal incubation systems. The addition of isolated rat liver ferritin augmented diquat-mediated oxidative damage in a time- and concentration-dependent manner, and the inclusion of deferoxamine completely inhibited the stimulation by ferritin. The results indicate that availability of ferritin iron is an important determinant of diquat-mediated oxidative injury and support the hypothesis that elevated hepatic ferritin content is responsible, at least in part, for the age-associated enhancement of diquat-induced toxicity.
ISSN:0003-9861
1096-0384
DOI:10.1006/abbi.1997.0172