Free Radical Scavenging and Antioxidant Activity of Allopurinol and Oxypurinol in Experimental 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. Invest Ophthalmol Vis Sci. 1994; 35:3897-
3904.