Abstract
The 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 and 10 µM) with diclofenac markedly
ameliorates the mitochondrial toxicity effects in rat hart mitochondria. In
this study, we showed that DIC impairs mitochondrial function and induces
mitochondrial toxicity in rat heart isolated mitochondria, which were
ameliorated by calcitriol. These findings suggest that calcitriol may be a
preventive/therapeutic strategy for cardiotoxicity complications
caused by DIC.
Key words
diclofenac - calcitriol - vitamin D - mitochondria - cardiotoxicity
