Endotoxin-induced mortality in rats is reduced by nitrones.
The goal of these investigations was to determine if nitrone spin-trapping agents can alter mortality associated with endotoxemia in the rat. Reactive free radicals attack nitrone spin-trapping agents forming relatively reactive, persistent free radical spin adducts. We administered 85 mM (10 ml/kg) of alpha-phenyl N-tert-butyl nitrone (PBN), alpha-4-pyridyl-N-oxide N-tert-butyl nitrone (4-POBN), 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), or vehicle (saline i.p.) 30 min before endotoxin (25 mg/kg i.p.) or vehicle to Sprague-Dawley (SD) or Holtzman virus-free (HVF) rats (n = 10-17/group). All vehicle-treated rats receiving endotoxin were dead by 1 day. At 7 days, 83% of PBN-treated SD, 42% of PBN- or POBN-treated HVF, and 25% of DMPO-treated HVF rats were alive. The difference in survival of PBN-treated animals between strains may reflect the higher susceptibility of HVF rats to endotoxin. The observed reduction in mortality may be related to the well-established capacity of spin-trapping agents to capture reactive free radicals that may be generated in target tissues in response to endotoxin, and that would otherwise react with cell components and produce tissue injury.
Hamburger
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Molecular Toxicology Research Group, Oklahoma Medical Researh Foundation, Oklahoma City 73104.
McCay
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D000818:Animals; D004927:Escherichia coli Infections / Q000188:drug therapy*; D008070:Lipopolysaccharides; D008297:Male; D009589:Nitrogen Oxides / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality
D008070:Lipopolysaccharides; D009589:Nitrogen Oxides; C015388:nitrones