Zileuton, a\n5‑Lypoxigenase Inhibitor, is Antiparasitic\nand Prevents Inflammation in the Chronic Stage of Heart Chagas Disease

Chronic Chagas cardiomyopathy is associated with an unbalanced\nimmune response and impaired heart function, and available drugs do\nnot prevent its development. Zileuton (Zi), a 5-lypoxigenase inhibitor,\naffects inflammatory/pro-resolution mediators. Herein, Zi treatment\nin the early phase of infection reduced parasitemia associated mainly\nwith the direct effect of Zi on the parasite, and the enzyme epoxide\nhydrolase was the potential molecular target behind the trypanocidal\neffect. In the intermediate acute phase of infection, Zi reduced the\nnumber of innate and adaptive inflammatory cells, increased the level\nof SOCS2 expression in the heart associated with lower inflammation,\nand improved cardiac function. Zi treatment initiated in the chronic\nstage increased the level of SOCS2 expression in the heart, reduced\ninflammation, and improved cardiac function. Our data suggest that\nZi protects against Trypanosoma cruzi infection by acting directly on the parasite and reducing heart\ndamage and is a promising option for the treatment of Chagas disease.