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Prevention of hepatocyte injury and lipid peroxidation by iron chelators and α‐tocopherol in isolated iron‐loaded rat hepatocytes
Author(s) -
Sharma Bipin K.,
Bacon Bruce R.,
Britton Robert S.,
Park Chanho H.,
Magiera Christopher J.,
O'Neill Rosemary,
Dalton Nicholas,
Smanik Patricia,
Speroff Theodore
Publication year - 1990
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840120107
Subject(s) - lipid peroxidation , hepatocyte , deferoxamine , viability assay , chemistry , biochemistry , incubation , malondialdehyde , antioxidant , medicine , pharmacology , in vitro , biology
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, α‐tocopherol, also protected against lipid peroxidation and preserved cell viability over a 4‐hr incubation. The protective effects of iron chelators and α‐tocopherol support a strong association between iron‐dependent lipid peroxidation and hepatocellular injury in iron overload. (H EPATOLOGY 1990;12:31–39).