Efficacy of the antioxidant ebselen in experimental uveitis.
Inflammation results in the production of free radicals. In a model of experimental uveitis upon subcutaneous injection of endotoxin to Lewis rats, i.e., endotoxin-induced experimental uveitis (EIU), we have evaluated the status of the antioxidant capacity of ocular tissues. EIU results in a decrease of glutathione (GSH) content and glutathione peroxidase (GPx) activity in whole eye homogenates 24-h after endotoxin administration. Furthermore, an increase in malondialdehyde (MDA) content was observed in these same samples, thus confirming the involvement of oxidative stress in the pathophysiology of the process. In view of the ability of the antioxidant ebselen as GPx enzyme mimic, we tested the effect of the oral treatment with two doses of 100 mg/kg body weight of ebselen (first dose administered at the same time of endotoxin, and the second after 12 h). Ebselen administration normalized the GSH and MDA contents and protected the GPx activity of the EIU rat eyes. The GPx activity in the eye homogenate of the treated rats could be completely acounted for by the ebselen-dependent GPx-like activity, i.e., GPx activity measured in the acidic supernatant of the homogenate after neutralization. Unmodified ebselen was detected in whole eye homogenates, thus it shows for the first time the penetration of ebselen through the blood-aqueous and blood-retina barrier. The results herein may allow the proposal of ebselen as a suitable antiinflammatory agent in ocular tissues.
Bosch-Morell
F
F
Department of Physiology, School of Medicine & Dentistry, University of Valencia, Spain.
Romá
J
J
Puertas
F J
FJ
Marín
N
N
Díaz-Llopis
M
M
Romero
F J
FJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001393:Azoles / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D004731:Endotoxins / Q000633:toxicity; D004926:Escherichia coli; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D054833:Isoindoles; D008315:Malondialdehyde / Q000378:metabolism; D016566:Organoselenium Compounds / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001393:Azoles; D004731:Endotoxins; D005609:Free Radicals; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D008315:Malondialdehyde; C044101:endotoxin, Escherichia coli; D005979:Glutathione Peroxidase; D005978:Glutathione