Modulating xanthine oxidase activity: a promising therapeutic strategy to reduce the severity and associated inflammatory reactions in malaria infection

Malaria is a severe and often fatal disease that affects millions of people each year. More than fifty percent of human population worldwide is at risk of malaria. While antimalarial therapy is targeted at parasite elimination, the pathogenesis of malaria infection is particularly oxidative and inflammatory, involving the generation of reactive oxygen species (ROS). Xanthine oxidase (XO) is believed to be a potent source of ROS during malaria infection. ROS generated by this enzyme are a major contributor to oxidative stress and inflammation development. Consequently, free radical production and oxidative stress are responsible for the numerous complications in severe malaria. Therefore, effective treatment of the disease will require, in addition to the elimination of the parasite, a mechanism that reduces severe oxidative stress and inflammatory reactions associated with the disease. The pathophysiologic role of this enzyme is thus a potential target in malaria infection. Inhibition of XO activity is clinically effective in treating many inflammatory diseases, such as gout and prevention of cardiovascular disorders, therefore making this enzyme an attractive candidate for treating malaria inflammation. The present review focuses on the role of XO in malaria pathogenesis and the potential of enzyme inhibition as a therapeutic strategy to mitigate the severe inflammatory responses during malaria infection. Ultimately, the severity, complications and death associated with the disease are ameliorated by reducing the intensity of the inflammatory reactions during malaria infection.

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