Different roles for nitrogen monoxide and peroxynitrite in lipid peroxidation induced by activated neutrophils.
We studied the roles of nitrogen monoxide (NO&z.rad;) and peroxynitrite produced by the polymorphonuclear leukocytes (PMNs) isolated from an inflammatory exudate. PMNs were incubated either in a medium with a submicromolar concentration of iron or in a diethylenetriaminepenta-acetic acid (DTPA)-containing medium, and stimulated with phorbol 12-myristate 13-acetate (PMA) to generate free radicals. In both conditions superoxide anion (O(2)(*)(-)), NO&z.rad; and peroxynitrite were produced. In the presence of arachidonic acid, malondialdehyde (MDA) was generated. This MDA was generated in one of two way; the peroxynitrite iron-independent mechanism (40%) and the Fenton reaction, caused by free iron (60%). We also observed that the addition of L-arginine was followed by a 42% reduction in MDA, which can be explained by the antioxidant effect of NO&z.rad;. These results indicate that lipid peroxidation can occur in the absence of iron, through a peroxynitrite-mediated mechanism, and that NO&z.rad; may act as an antioxidant when it is produced in large amounts.
Ródenas
J
J
Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
Carbonell
T
T
Mitjavila
M T
MT
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002351:Carrageenan; D003676:Deferoxamine / Q000494:pharmacology; D005122:Exudates and Transudates; D006099:Granuloma / Q000139:chemically induced / Q000503:physiopathology; D007249:Inflammation; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009566:Nitrates / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D016877:Oxidants / Q000502:physiology; D004369:Pentetic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D009566:Nitrates; D016877:Oxidants; D013481:Superoxides; C039642:peroxynitric acid; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D008315:Malondialdehyde; D004369:Pentetic Acid; D002351:Carrageenan; D001120:Arginine; D009952:Ornithine; D013482:Superoxide Dismutase; D003676:Deferoxamine