Effect of allopurinol on cardiomyocyte apoptosis in rats after myocardial infarction.

Aims: This study was designed to explore the effect of the xanthine oxidase (XO) inhibitor allopurinol on cardiomyocyte apoptosis after myocardial infarction (MI) in a rat model.

Methods And Results: MI was induced in rats by ligation of the anterior descending coronary artery. Survivors were randomly divided into three groups: sham operation group, MI group, and allopurinol group (50 mg kg(-1) day(-1)). After 28 days, infarction size was measured. In non-infarcted zones (NIZ), apoptosis index (AI) was measured by TUNEL [terminal deoxynucleotidyl transferase (TdT)-mediated digoxigenin-conjugated dUTP nick-end labelling]; expression of Fas was detected by immunohistochemistry, and expression of XO and Caspase-3 by western blot. In addition, XO and O(2)(-), OH-scavenging activity of myocardial tissue in the NIZ were measured by colorimetry. Results suggest that AI and expression of Fas and Caspase-3 in the NIZ were significantly depressed in the allopurinol group, compared with MI group; moreover, activity of XO was significantly decreased while O(2)(-) and OH-scavenging activity were significantly increased in the allopurinol group. Ventricular remodelling was attenuated but there were no significant differences in infarct size or XO expression levels between the allopurinol and MI groups.

Conclusion: Our results suggest that allopurinol may inhibit cardiomyocyte apoptosis in the NIZ in rats. The potential mechanism could be related to its ability to reduce reactive oxygen species and to depress the expression of Fas and Caspase-3.