Reactive oxygen species produced by liver mitochondria of rats in sepsis.
Reactive oxygen species (ROS) can be generated in experimental shock states through several different mechanisms. We measured ROS production in metabolically active liver mitochondria from rats rendered septic by cecal ligation and puncture. By polarography, the State 4 and State 3 respiration rates of liver mitochondria isolated from septic animals were no different from control organelles. During oxidation of succinate, however, nonenzymatic hydroxylation of salicylic acid to 2,3-dihydroxybenzoic acid by mitochondria from septic rats was increased, indicating generation of hydroxyl radical (OH.). Inhibition of electron transport at Complex I with rotenone had no effect on this pattern of OH. production, but rotenone and cyanide abolished the differences in OH. formation between control and septic liver mitochondria. Measurements of H2O2 release suggested that septic mitochondria will increase rates of H2O2 production in the presence of succinate. Additional investigations revealed no difference in the release of iron between septic and control mitochondria. When referenced to respiration rate, both OH. and H2O2 production were greater in septic liver mitochondria. The reproducible effect of sepsis on generation of reactive oxygen species by liver mitochondria utilizing FAD-linked but not NAD-linked substrates suggests that enhanced mitochondrial oxidative stress in sepsis is related to alterations in the activity of Complex II of the electron transport chain.
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
D E
DE
Taylor
A J
AJ
Ghio
C A
CA
Piantadosi
D000818:Animals; D002474:Cell-Free System; D003486:Cyanides / Q000494:pharmacology; D004579:Electron Transport; D006861:Hydrogen Peroxide / Q000378:metabolism; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D018384:Oxidative Stress; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012402:Rotenone / Q000494:pharmacology; D012459:Salicylates / Q000378:metabolism; D020156:Salicylic Acid; D018805:Sepsis / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid
D003486:Cyanides; D062385:Hydroxybenzoates; D017382:Reactive Oxygen Species; D012459:Salicylates; D013386:Succinates; D012402:Rotenone; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D019802:Succinic Acid; D006861:Hydrogen Peroxide; D007501:Iron; D020156:Salicylic Acid