Lipid emulsion inhibits the cardiac toxicity caused by chloroquine via inhibition of reactive oxygen species production

Abstract

Background: Lipid emulsion (LE) is effective in treating intractable cardiac depression in-duced by the toxicity of highly lipid-soluble drugs including local anesthetics. However, the effect of LE on chloroquine (CQ)-evoked cardiac toxicity remains unclear. This study aimed to examine the effect of Lipofundin MCT/LCT, an LE, on the cardiotoxicity caused by CQ in H9c2 rat cardiomyoblasts and elucidate the underlying cellular mechanism.Methods: The effects of CQ (1 x 10-4 M), LE, and the reactive oxygen species (ROS) scav-engers mitotempo and N-acetyl-L-cysteine (NAC), alone or combined, on cell viability and migration, apoptosis, ROS production, calcium levels, mitochondrial membrane po-tential, and adenosine triphosphate (ATP) were examined. Additionally, the effects of LE on the activities of catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD) induced by CQ were assessed.Results: Pretreatment with LE, mitotempo, or NAC reversed the reduction in cell migra-tion and viability, mitochondrial membrane potential, and ATP levels evoked by CQ, and inhibited the increase in cleaved caspase-3, ROS, and calcium concentration induced by CQ. LE inhibited the increase in Bax expression, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, MDA activity, and late apoptosis, and reversed the reduction in SOD and CAT activity induced by CQ. CQ did not significantly affect cleaved caspase-8 expression, and LE did not significantly affect CQ concentration.Conclusions: Collectively, these results suggest that LE (Lipofundin MCT/LCT) inhibits the cardiotoxicity and late apoptosis induced by CQ toxicity via the intrinsic mitochondri-al apoptotic pathway that is associated with direct inhibition of ROS production.