Background: 

We showed that xanthine oxidase activity increases in the liver and plasma of type I diabetic animals and that this is a significant cause of the oxidative stress which occurs in the disease.

Aim: 

To search for molecular links between xanthine oxidase-induced oxidative stress and inflammation in Type I diabetes and to assess the ability of allopurinol, a drug widely used to treat hyperuricemia, to prevent both processes.

Methods: 

3-month-old male Wistar rats were made diabetic by injection (i.p.) of either streptozotocin or alloxan. Allopurinol (32 mg.kg^-1) was administered (i.p. or per os) to diabetic rats 12 or 28 days after they had shown signs of diabetes.

Results: 

Hepatic phospho-IKKb and phospho-IkBa contents were increased in the diabetic animals. This was accompanied by increased levels of NF-kB (p65 protein content) in liver nuclear extracts. As a direct consequence, the hepatic expression of NF-kB dependent inflammatory cytokines and enzymes, namely interleukin 1b, interleukin 6, inflammatory nitric oxide synthases (iNOS) and cyclooxigenase 2 (COX-2), were markedly increased. Both diabetes-induced activation of NF-kB signalling cascade and subsequent over expression of inflammatory cytokines and enzymes were abolished by administration of allopurinol. Moreover, we found a significant neutrophil infiltration in the liver of diabetic animals and signs of hepatic damage (evidenced by histological examination as well as by an increase in plasma alanine-amino transferase activity). These events were also prevented by administration of allopurinol.

Conclusions: 

These results open up the possibility of treating inflammatory long term complications of diabetes with allopurinol.