Chlordecone (kepone) induces mitochondrial dysfunction in human cardiac tissue

Chlordecone exposure in humans has been associated with increased incidence of prostate cancer, impaired fertility, and fetal/perinatal abnormalities while experiment rodent studies suggest that chlordecone can inhibit magnesium-ATPase, little is known about its mitochondrial toxicity in humans. Our objective was to test whether chlordecone would induce mitochondrial dysfunction in human cardiac cells in ex vivo heart preparations. Biopsies of human atrial tissue were obtained during cannulation for cardiopulmonary bypass from patients who were undergoing programmed cardiac surgery for coronary artery bypass. Cardiac preparations were incubated with vehicle or chlordecone (5 nM and 50 nM) for 24 hr followed by mitochondrial high-resolution oxygraphy studies. Compared with vehicle, chlordecone cardiac exposure at the concentrations of 5 nM and 50 nM impaired mitochondrial respiratory rates. Chlordecone concentrations of 5 nM and 50 nM similarly increased state 2 respiration rate and maximal respiration capacity with no change of state 3 (ADP) respiration rate, which suggests the uncoupling of between mitochondrial oxidative phosphorylation and electron transport through the respiratory chain complexes. In conclusion, our study suggests that chlordecone at clinically relevant concentration impairs mitochondrial function leading to uncoupling, which may induce abnormal cardiac cell responses, including aberrant calcium handling and oxidative stress.