Free radical scavenging and antioxidant activity of allopurinol and oxypurinol in experimental lens-induced uveitis.
OBJECTIVE
In addition to the inhibition of xanthine oxidase, allopurinol is known to act, dependent on the dose, as a free radical scavenger, an antioxidant, and a "scavenger" of hypochlorous acid. This activity was investigated using a model of lens-induced uveitis.


METHODS
Lipid peroxides (LPO) were determined in aqueous humor and in retinal tissue. Reduced and oxidized glutathione (GSH and GSSG) of the aqueous humor and myeloperoxidase (MPO) activity in the iris-ciliary body complex were analyzed. Allopurinol and oxypurinol concentrations were determined by high-performance liquid chromatography in aqueous humor and retinal tissue of both control eyes and eyes with uveitis. These measurements were performed 6 hours after intravenous application of allopurinol.


RESULTS
In lens-induced uveitis, LPO are significantly elevated, GSH is reduced, and GSSG and MPO are increased. A xanthine oxidase inhibition dose (< 10 mg/kg body weight) of allopurinol showed no effects on oxidative tissue damage in the model used in this study. Higher doses, however, were able to reduce the oxidative damage. Allopurinol (20 mg/kg body weight) had slight effects on GSH and GSSG. All parameters improved using a dose of 50 mg/kg body weight; a dose of 100 mg/kg body weight only showed additional improvement in GSH and GSSG. There was no further change in the other parameters. Allopurinol and oxypurinol concentrations in aqueous humor and retinal tissue showed a dose dependency reaching scavenger concentrations after application of 50 mg/kg body weight of allopurinol.


CONCLUSIONS
These results suggest that the xanthine oxidase mechanism plays a minor role in the oxidative tissue damage due to lens-induced uveitis. Free radicals and oxidants are generated by activated leukocytes; therefore, the effect of higher doses of allopurinol is due to its free radical scavenging and antioxidative activity.
Augustin
A J
AJ
University Eye Hospital, University of Bonn, Germany.
Böker
T
T
Blumenröder
S H
SH
Lutz
J
J
Spitznas
M
M
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D000869:Anterior Eye Segment / Q000378:metabolism; D000975:Antioxidants; D002851:Chromatography, High Pressure Liquid; D003459:Crystallins; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers; D005978:Glutathione / Q000378:metabolism; D007908:Lens, Crystalline; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D010117:Oxypurinol / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*
D000975:Antioxidants; D003459:Crystallins; D016166:Free Radical Scavengers; D008054:Lipid Peroxides; D000493:Allopurinol; D009195:Peroxidase; D010117:Oxypurinol; D005978:Glutathione