MARBOFLOXACIN INDUCES LEISHMANICIDAL ACTIVITY AND LESS INFLAMMATORY RESPONSE IN Leishmania chagasi INFECTED MACROPHAGES

Marbofloxacin has promising leishmanicidal activity due to the direct action on the Leishmania chagasi amastigotes. It was developed only for veterinary medicine uses, and it could be used as an drug for the treatment of Canine Visceral Leishmaniasis (CVL). In the present study, we evaluated the leishmanicidal effect and macrophage modulation of marbofloxacin in macrophages infected with amastigotes of L. chagasi. Macrophages were collected from peritoneum of BALB/c mice and infected with promastigotes of L. chagasi. After internalization and transformation into amastigotes forms, cells were treated with marbofloxacin in concentration of 100, 500 and 750 μg/mL for 18 hours. The leishmanicidal effect was evaluated by morphological spects of amastigotes inside of macrophages by phagocytosis assay and detection of death amastigotes and macrophages by TUNEL assay. Macrophage modulation was evaluated by release of cytotoxic metabolites and cytokine production. The results showed that L. chagasi-infected macrophages treated with the highest concentration of the drug showed lower amount of amastigotes into the macrophages (p<0,0632) than untreated infected cells. There was pronounced presence of cellular vacuoles in the treated infected-cells, and more apoptotic amastigotes in alive macrophages. It was observed decreased levels of H2O2, IL-1β, IL-6, and TNF-α dose-dependent of marbofloxacin in infected macrophages. The results indicate the leishmanicidal effect of marbofloxacin in infected macrophages and immunomodulation actions in these cells.