EPR studies of in vivo radical production by lipopolysaccharide: potential role of iron mobilized from iron-nitrosyl complexes.
Although oxidative stress has been implicated in the pathogenesis of sepsis, there is little evidence for the formation of radicals other than nitric oxide in its experimental models. Here we used low temperature EPR and EPR spin trapping to monitor nitric oxide and secondary radical formation in blood, liver, and bile samples from rats treated with a low lipopolysaccharide (LPS) dose (0.25 mg) and with dimethyl sulfoxide (DMSO) and the spin trap alpha-(4-pyridyl 1-oxide)- N-t-butylnitrone (POBN). The results showed that production of secondary radicals triggered by LPS is delayed in regard to maximum nitric oxide synthesis and is iron-dependent. One of the secondary produced radicals was identified as the hydroxyl radical. Its formation is proposed to occur because of the mobilization of redox-active iron required to repair the nitrosyl complexes produced by LPS. The results suggest that iron chelation may be a useful adjuvant therapy for treating sepsis.
Linares
Edlaine
E
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
Nakao
Lia S
LS
Augusto
Ohara
O
Kadiiska
Maria B
MB
D000818:Animals; D001646:Bile / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000494:pharmacology; D010084:Oxidation-Reduction; D011725:Pyridines; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels
D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D008070:Lipopolysaccharides; D009589:Nitrogen Oxides; D011725:Pyridines; D013113:Spin Labels; C043438:alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; D009569:Nitric Oxide; D017665:Hydroxyl Radical; C073661:dinitrosyl iron complex; D007501:Iron; D004121:Dimethyl Sulfoxide