Xanthine oxidoreductase (XOR) is a rate-limiting enzyme of purine catabolism that is found in two forms, as xanthine dehydrogenase (XD) and xanthine oxidase (XO). XOR, particularly in the XO form, generates reactive oxygen species such as O2-, hydroxyl radicals and H2O2. Experimental and clinical researchs have implicated XO in oxidation stress-related diseases. One of the most widely accepted theories proposed to explain ageing is the free radical theory, according to which oxygen-derived free radicals cause age-related impairment through oxidative damage to biomolecules.

In this study, we investigate the changes in XO activity and lipid peroxidation in two brain areas (cerebral cortex and brain stem) from adult mice (6 month-old) and old mice (18 month-old). Lipid peroxidation was determined by the thiobarbituric acid-reactive substances (TBARs) assay. XO activity of tissue samples was determined using the "Amplex Red Xathine/XO Assay" kit (Molecular Probes). TBARs production was significantly higher in the cerebral cortex in old-mice compared to adult-mice (9.17±1.70 vs 6.95±1.30 nmolMDA/mg protein, p<0.05, respectively).In brain stem there was no differences in TBARs production between the two groups. XO activity was significantly increased in the cerebral cortex of old mice (46.9±14 vs 37.16±17 mU/mg protein, p<0.05, in old and adult mice,respectively). However no significantly differences were observed in brain stem. In summary, we have shown that TBARs levels and XO activity increase in the cerebral cortex of old animals. The oxidative damage in this area of the brain could be responsible of several age-related physiological dysfunctions.

Financial support: MEC (BFU2005-06777) grant.