The selective protection afforded by ebselen against lipid peroxidation in an ROS-dependent model of inflammation.
The effects of an experimental model of hydrogen-peroxide-induced foot pad oedema on indices of oxidative damage to biomolecules have been investigated. We have demonstrated increased levels of fluorescent protein and lipid peroxides occurring in plasma at 24 and 48 h post-injection. In addition, a decrease in the degree of galactosylation of IgG was observed which kinetically related the degree of inflammation and to the increase in protein autofluorescence (a specific index of oxidative damage). The effects of ebselen, a novel organoselenium compound which protects against oxidative tissue injury in a glutathione-peroxidase-like manner, have also been examined in this model. Pretreatment of animals with a dose of 50 mg/kg ebselen afforded significant and selective protection against lipid peroxidation only. This effect may contribute to the anti-inflammatory effect of this agent in hydroperoxide-linked tissue damage.
Griffiths
H R
HR
Molecular Toxicity Group, Glenfield General Hospital, Leicester, UK.
Dowling
E J
EJ
Sahinoglu
T
T
Blake
D R
DR
Parnham
M
M
Lunec
J
J
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D016166:Free Radical Scavengers; D005690:Galactose / Q000378:metabolism; D005949:Glucose Oxidase / Q000494:pharmacology; D006861:Hydrogen Peroxide; D007074:Immunoglobulin G / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D054833:Isoindoles; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001393:Azoles; D016166:Free Radical Scavengers; D007074:Immunoglobulin G; D054833:Isoindoles; D008054:Lipid Peroxides; D016566:Organoselenium Compounds; C042986:ebselen; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D005690:Galactose