Trivalent and Pentavalent Antimonials Impair Cardiac Mitochondrial Function in Mice

Area of Science:

• Biochemistry
• Pharmacology
• Cell Biology

Background:

• Pentavalent sodium antimoniate (Sb(V)) is a long-standing treatment for leishmaniasis.
• Sb(V) acts as a prodrug, converting to Sb(III) within macrophages to disrupt parasite energy metabolism.
• The impact of antimonials on host cell mitochondria remains poorly understood.

Purpose of the Study:

• To investigate the direct effects of Sb(V) and Sb(III) on isolated mouse heart mitochondria.
• To evaluate the functional consequences of antimonial exposure on mitochondrial respiration, ATP production, ROS generation, and membrane potential.

Main Methods:

• Mitochondria were isolated from mouse hearts using differential centrifugation.
• Isolated mitochondria were incubated with Sb(V) or Sb(III) at varying concentrations.
• Mitochondrial function was assessed by measuring oxygen consumption, ATP production, ROS generation, and transmembrane potential.

Main Results:

• Both Sb(V) and Sb(III) significantly reduced mitochondrial oxygen consumption at concentrations of 1 µg/mL and 1 ng/mL.
• Sb(V) treatment led to increased reactive oxygen species (ROS) production.
• ATP production was impaired by both Sb(V) and Sb(III) starting at 1 ng/mL, with increased proton leak and altered transmembrane potential observed.

Conclusions:

• Sb(V) and Sb(III) directly impair the function of isolated mouse heart mitochondria.
• Antimonial treatment compromises mitochondrial energy production by reducing ATP synthesis.
• Increased ROS generation and altered mitochondrial membrane potential suggest potential cardiotoxicity associated with antimonial drugs.