Objectives: 

The liver is vulnerable to oxidative stress on account of the high rate of oxygen utilization. In previous studies, an increased xanthine oxidase (XO) activity, a critical source of oxidants, has been observed in the liver from old mice. In this work, we investigated the effects of XO inhibition with allopurinol on the oxidative stress status in the liver from old prematurely (PAM) and non-prematurely (NPAM) aging mice.

Materials: 

Old female BALC/c mice were classified as NPAM and PAM based on their different behavioral response in a T-maze test. Both groups of mice were divided randomly into 2 experimental groups. One served as control (NPAMc/PAMc), whereas the other was treated with allopurinol (1mmol/L in drinking water; 12 weeks). After treatment (24 month-old), the XO activity in the liver was measured using a commercial kit, whereas the XO expression was detected by western blot. The catalase (CAT) and superoxide dismutase (SOD) activities were determined using spectrophotometric methods. Statistical analysis was performed using Student´s t-test.

Results: 

In the liver, PAMc showed a significant increase in both XO activity (p<0.01) and expression (p<0.05), as well as a decreased CAT (p<0.01) and SOD (p<0.05) activities with respect to NPAMc. The treatment with allopurinol decreased significantly the XO activity/expression in the liver from PAM (p<0.001/p<0.01) and NPAM (p<0.01/p<0.05) in comparison with their respectives control groups (PAMc and NPAMc). Moreover, allopurinol treatment increased significantly the CAT activity (p<0.05) in NPAM and both CAT (p<0.01) and SOD (p<0.05) activities in PAM.

Conclusions: 

In a model of premature aging in mice, XO inhibition with allopurinol specially decreases the oxidative stress status, measured as XO/SOD-CAT, in the liver from old PAM. These findings suggest that allopurinol protects against oxidative damage caused by aging in the liver from old mice. Support: MCINN(BFU2011-30336), UCM-Research-Group(910379), RETICEF(RD06/0013/0003)