Iron and oxidative stress in cold-initiated necrotic death of rat hepatocyte.
Iron chelators and antioxidants have been shown to prevent hypothermia-induced apoptosis in hepatocytes. This study examined whether iron chelation and antioxidants could also prevent hypothermia-induced necrosis. Isolated rat hepatocytes were incubated at 4 degrees C for 6 hours and then rewarmed at 37 degrees C for 18 hours with or without the iron chelator deferoxamine and a selection of antioxidants. There was no evidence of increased cell death or adenosine triphosphate depletion during hypothermic incubation. After hypothermia and rewarming, the majority of rat hepatocytes died of necrosis as indicated by the absence of DNA fragmentation, caspase 3 activity, and apoptotic bodies. Cell death was significantly reduced if deferoxamine or a selection of antioxidants were present during hypothermia and rewarming. Deferoxamine was more effective in preventing cell death when added prior to hypothermia, indicating cell death processes were likely initiated during hypothermia.
Niu
X
X
School of Medicine and Pharmacology University of Western Australia, Crawley, Western Australia. xianwa@cyllene.uwa.edu.au
Arthur
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PG
Jeffrey
G P
GP
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001205:Ascorbic Acid / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007035:Hypothermia / Q000473:pathology; D007501:Iron / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D007773:Lactates / Q000378:metabolism; D009336:Necrosis; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats
D007773:Lactates; D000255:Adenosine Triphosphate; D007501:Iron; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D001205:Ascorbic Acid