Celecoxib decreases mitochondrial complex IV activity and induces oxidative stress in isolated rat heart mitochondria: An analysis for its cardiotoxic adverse effect.

Abstract

In spite of the cardiotoxic effect of selective cyclooxygenase-2 inhibitors, they are most widely used as anti-inflammatory and analgesic drugs. Today, valdecoxib and rofecoxib have been withdrawn in the market but celecoxib remains. In this study, we focused on an analysis of celecoxib toxic effects on isolated mitochondria. Isolated rat heart mitochondria were obtained using differential centrifugation. Using flow cytometry and biochemical assays, we searched succinate dehydrogenases, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) formation, mitochondrial swelling, ATP/ADP ratio, lipid peroxidation, and mitochondrial complexes activity in rat heart isolated mitochondria. Herein, our results indicated a significant decrease in the activity of complex IV after exposure with celecoxib (16 µg/ml). This decrease in the activity of complex IV is paralleled by the MMP collapse, ROS formation, mitochondrial swelling, depletion of ATP, and lipid peroxidation. For the first time, this introductory study has shown a significant decrease in the activity of complexIV and mitochondrial dysfunction after exposure with celecoxib in rat heart isolated mitochondria.