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 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.
Rikans
L E
LE
University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA. lora-rikans@uokhsc.edu
Ardinska
V
V
Hornbrook
K R
KR
D000375:Aging / Q000378:metabolism*; D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology; D004178:Diquat / Q000633:toxicity*; D005293:Ferritins / Q000737:chemistry / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009929:Organ Size; D018384:Oxidative Stress; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D011506:Proteins; D009249:NADP; D005293:Ferritins; D004178:Diquat; D007501:Iron; D009245:NADH Dehydrogenase; D003676:Deferoxamine