Free radicals and septic shock in primates: the role of tumor necrosis factor.
The role of free radicals in septic-shock-associated tissue injury and the mechanisms underlying the generation of free radicals in sepsis was investigated in a primate model using electron spin resonance (ESR) spectroscopy and spin-trapping techniques paired with physiological measurements. Baboons were administered the spin trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) during infusions of live Escherichia coli (E. coli) with or without challenge with tumor necrosis factor (TNF). ESR spectra suggesting the trapping of carbon-centered and oxygen-centered radicals were detected in liver lipid extracts of E. coli infused animals which exhibited pathophysiological changes indicative of sepsis. In animals demonstrating a toxic response to E. coli. TNF challenge appeared to intensify the ESR signal observed. These data provide evidence of free radical production during sepsis and suggest a role for TNF in the production of these radicals.
Molecular Toxicology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
S S
SS
Lloyd
A K
AK
Chang
F B
FB
Taylor
E G
EG
Janzen
P B
PB
McCay
D000818:Animals; D016470:Bacteremia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure; D003497:Cyclic N-Oxides; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy; D004927:Escherichia coli Infections / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D005609:Free Radicals / Q000378:metabolism*; D006339:Heart Rate; D007958:Leukocyte Count; D008099:Liver / Q000378:metabolism; D010215:Papio; D012772:Shock, Septic / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D013113:Spin Labels; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D003497:Cyclic N-Oxides; D005609:Free Radicals; D013113:Spin Labels; D014409:Tumor Necrosis Factor-alpha; C017245:5,5-dimethyl-1-pyrroline-1-oxide