Calcitriol Reduces Adverse Effects of Diclofenac on Mitochondrial Function in Isolated Rat Heart Mitochondria

Drug Res (Stuttg) DOI: 10.1055/a-1167-0691The safety of diclofenac (DIC) use in clinical practice has been questioned because of adverse cardiovascular effects. Previous studies have indicated that DIC cause mitochondrial dysfunction and oxidative stress in heart mitochondria. The aim of this study was to investigate the protective effect of calcitriol against the mitochondrial toxicity potency of diclofenac in heart rat mitochondria. For this purpose, rat heart mitochondria were isolated with mechanical lysis and differential centrifugation. Then isolated mitochondria were pretreated with 3 different concentrations of calcitriol (2.5, 5 and 10 µM) for 5 min at 37°C, after which DIC (10 µg/ml) was added to promote deleterious effects on mitochondria. During 1 hour of incubation, using by flow cytometry and biochemical evaluations, the parameters of mitochondrial toxicity were evaluated. Our results showed that DIC (10 µg/ml) caused a significant decrease in succinate dehydrogenase (SDH) activity, mitochondrial membrane potential (MMP) collapse, and mitochondrial swelling, and a significant increase in reactive oxygen species (ROS) formation, lipid peroxidation (LP) and oxidative stress. Also, our results revealed that co-administration of calcitriol (5...
Source: Drug Research - Category: Drugs & Pharmacology Authors: Tags: Original Article Source Type: research