Desferal prevents against cell lysis induced by hydrogen peroxide to hypoxic hepatocytes: a role for free iron in hypoxia-mediated cellular injury.
Isolated hepatocytes incubated under hypoxic conditions were more sensitive to H2O2-mediated injury as compared to cells kept under aerobic conditions, but only for the highest H2O2 concentration tested (8 mM). At lower concentrations (2 and 4 mM) cells were still able to detoxify H2O2 even under hypoxic conditions. Reoxygenation of hypoxic hepatocytes did not result in a cytolytic effect, whereas reoxygenation in the presence of H2O2 resulted in an enhanced cytotoxicity. The duration of previous hypoxia (before H2O2 addition) did not affect the lytic effect induced by H2O2. Enzymatic activities of both catalase and glutathione peroxidase were unchanged over 2 h of incubation under hypoxic conditions. Preincubation of hepatocytes in the presence of Desferal (5 mM) resulted in the abolition of H2O2-mediated lytic effects. A role for free iron, released from intracellular stores and acting on H2O2 to yield reactive oxygen species is discussed.
Lefebvre
V
V
Département des Sciences Pharmaceutiques, Université Catholique de Louvain, Bruxelles, Belgium.
Buc-Calderon
P
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D015687:Cell Hypoxia; D003676:Deferoxamine / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007501:Iron / Q000502:physiology*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D007501:Iron; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D003676:Deferoxamine