Prevention of hepatocyte injury and lipid peroxidation by iron chelators and alpha-tocopherol in isolated iron-loaded rat hepatocytes.
These experiments were performed to characterize the relationship between lipid peroxidation and hepatocyte viability in iron overload. Hepatocytes were isolated from rats with chronic dietary iron overload and the effects of in vitro iron chelation on lipid peroxidation, cell viability and ultrastructure were studied over a 4-hr incubation period. Cell viability was significantly reduced at 3 and 4 hr in iron-loaded hepatocytes compared with controls and was preceded by an increase in iron-dependent lipid peroxidation. Similarly, extensive degenerative ultrastructural changes were observed in iron-loaded hepatocytes compared with controls after 4 hr of incubation. In vitro iron chelation with either deferoxamine or apotransferrin protected against lipid peroxidation, loss of viability and ultrastructural damage in iron-loaded hepatocytes. The addition of an antioxidant, alpha-tocopherol, also protected against lipid peroxidation and preserved cell viability over a 4-hr incubation. The protective effects of iron chelators and alpha-tocopherol support a strong association between iron-dependent lipid peroxidation and hepatocellular injury in iron overload.
Sharma
B K
BK
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland Metropolitan General Hospital, Ohio 44109.
Bacon
B R
BR
Britton
R S
RS
Park
C H
CH
Magiera
C J
CJ
O'Neill
R
R
Dalton
N
N
Smanik
P
P
Speroff
T
T
D000818:Animals; D001059:Apoproteins / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology*; D007501:Iron / Q000494:pharmacology* / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014168:Transferrin / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*
D001059:Apoproteins; D014168:Transferrin; C028284:apotransferrin; D014810:Vitamin E; D008315:Malondialdehyde; D007501:Iron; D003676:Deferoxamine