Role of oxygen and nitrogen species in experimental uveitis: anti-inflammatory activity of the synthetic antioxidant ebselen.
This study was aimed at examining the role of oxygen and nitrogen reactive species in a model of experimental uveitis upon intravitreal injection of bacterial endotoxin to albino New Zealand rabbits. The inflammatory response was evaluated in terms of: (i) the integrity of the blood aqueous barrier (protein and cell content in samples of aqueous humor), (ii) histopathological changes of the eyes, (iii) clinical evaluation (with a score index based on clinical symptoms), and (iv) the concentration of malondialdehyde (MDA), in aqueous humor, as a marker of oxidative stress. Betamethasone was used as reference treatment, superoxide dismutase as quencher of superoxide anion, L-N(G)-nitro-L-arginine-methyl-esther (L-NAME) and chlorpromazine as nitric oxide synthase inhibitors, and ebselen, a glutathione peroxidase mimic, as peroxynitrite reductant. All the substances were injected subconjunctivally to the rabbits immediately after the intravitreal endotoxin injection. Ebselen was the only treatment able to decrease MDA concentration to control values, exerting an effect similar to that elicited by L-NAME on the rest of the parameters tested. The data presented render ebselen a notable choice for the treatment of uveitis, with implications for clinical trials.
Department of Physiology, Pharmacology, and Toxicology, Universidad Cardenal Herrera-CEU, Valencia, Spain.
Francisco
F
Bosch-Morell
Joaquín
J
Romá
Nuria
N
Marín
Belén
B
Romero
Antonio
A
Rodriguez-Galietero
Siv
S
Johnsen-Soriano
Manuel
M
Díaz-Llopis
Francisco J
FJ
Romero
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals; D054833:Isoindoles; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D016566:Organoselenium Compounds / Q000494:pharmacology*; D011817:Rabbits; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D014605:Uveitis / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001393:Azoles; D004791:Enzyme Inhibitors; D005609:Free Radicals; D054833:Isoindoles; D016566:Organoselenium Compounds; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C042986:ebselen; D008315:Malondialdehyde; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D002746:Chlorpromazine; D019331:NG-Nitroarginine Methyl Ester