Gallic acid inhibits celecoxib-induced mitochondrial permeability transition and reduces its toxicity in isolated cardiomyocytes and mitochondria.

Abstract

Mitochondria are the main target organelles through which drugs and chemicals exert their toxic effect on cardiomyocytes. The mitochondria-related mechanisms of celecoxib-induced cardiotoxicity have been extensively studied. Accumulated evidence shows natural molecules targeting mitochondria have proven to be effective in preventing cardiotoxicity. In the present study, we examined the ameliorative effect of gallic acid (GA) against celecoxib-induced cellular and mitochondrial toxicity in isolated cardiomyocytes and mitochondria. The isolated cardiomyocytes and mitochondria were divided into various group, namely, control, celecoxib, celecoxib + GA (10, 50, and 100µM). Several cellular and mitochondrial parameters such as cell viability, lipid peroxidation, succinate dehydrogenase (SDH) activity, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) collapse, and mitochondrial swelling were assessed in isolated cardiomyocytes and mitochondria. Our results showed that administration of celecoxib (16µg/ml) induced cytotoxicity and mitochondrial dysfunction at 6h and 1h, respectively, which is associated with lipid peroxidation intact cardiomyocytes, mitochondrial ROS formation, MMP collapse, and mitochondrial swelling. The cardiomyocytes and mitochondria treated with celecoxib + GA (10, 50, and 100µM) significantly and dose-dependently restore the altered levels of cellular and mitochondrial parameters. We concluded that GA through antioxidant potential and inhibition of mitochondrial permeability transition (MPT) pore exerted ameliorative role in celecoxib-induced toxicity in isolated cardiomyocytes and mitochondria. The data of the current study suggested that GA supplementation may reduce celecoxib-induced cellular and mitochondrial toxicity during exposure and may provide a potential prophylactic and defensive candidate for coxibs-induced mitochondrial dysfunction, oxidative stress, and cardiotoxicity.