Trivalent and Pentavalent Antimonials Impair Cardiac Mitochondrial Function in Mice

Pentavalent sodium antimoniate (Sb(V)) has been used for over 50 years in leishmaniasis treatment. Sb(V) is converted into trivalent antimony (Sb(III)) within macrophages acting as a prodrug by disrupting fatty acid beta-oxidation and glycolysis, impairing the energy metabolism of the parasite. Despite extensive use, the effects of antimonials on host mitochondria are not well understood. This study investigated the impact of Sb(V) and Sb(III) on mitochondria isolated from mouse hearts via differential centrifugation and lastly incubated with Sb(V) or Sb(III). Mitochondrial function was evaluated by oxygen consumption, ATP production, reactive oxygen species (ROS) generation, and transmembrane potential. Both Sb(V) and Sb(III) reduced oxygen consumption in complex I respiratory states 1, 2, and 3 at 1 µg/mL and 1 ng/mL. ROS production increased in Sb(V)-treated mitochondria. ATP production was impaired by both drugs starting at 1 ng/mL. Proton leak also increased, and significant changes in transmembrane potential were observed at both concentrations. These findings indicate that Sb(V) and Sb(III) directly compromise mitochondrial function from isolated mouse heart mitochondria by reduced ATP production and increased ROS.