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Biological markers of oxidative stress and allopurinol therapy: A meta-analysis of randomized controlled trials

Manal M. Alem

Aim: Oxidative stress contributes to the development of atherosclerosis via production of reactive oxygen species (ROS). Xanthine oxidase is an important enzyme that generates ROS and mediates oxidative modification of low-density lipoprotein (LDL) which is a key step in fatty streak and subsequent atheroma formation. Allopurinol is a xanthine oxidase inhibitor that has been shown to reduce the concentrations of the biological markers of oxidative stress. This meta-analysis was designed to summarize the effect of allopurinol treatment on markers of oxidative stress.

Methods: Medline, PubMed, Pro Quest Health & Medical Complete, Clinical Key, Wiley Online Library, and Cochrane Central Register of Controlled Trials were searched till 29^th July, 2017. Meta-analysis was planned for randomized controlled trials (RCTs) that investigated allopurinol effects on oxidative stress. A random-effect model was used to calculate the raw mean difference or the standardized mean difference (with 95% confidence intervals: CI) as an estimate of effect size. Heterogeneity was quantified by four types of information; Q-statistic, I² statistic, T², and T.

Results: 37 eligible studies were identified; 14 were included in the final analysis and subdivided between two oxidative stress markers: there were 8 Malondialdehyde (MDA)-based studies (198 subjects) and 6 oxidized Low-density lipoprotein (Ox-LDL)-based studies (347 subjects). Allopurinol treatment was associated with a statistically significant reduction in mean MDA serum concentration, by 0.403 nmol/ml (95% CI; -0.618, -0.189) (P<0.001) and a non-significant reduction in Ox-LDL serum concentration assessed by the standardized mean difference, by 0.409 (95% CI; -1.332, 0.515) (P=0.386).

Conclusion: The antioxidant potential of allopurinol has been confirmed by a significant reduction of the serum concentration of MDA in a heterogeneous group of patients and healthy adults. The non-significant reduction in Ox-LDL may reflect methodological differences. To confirm whether or not allopurinol has clinically relevant antioxidant properties, future studies require reproducible measurement techniques and clearer characterization and quantification in different patient groups.