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: Khezri, Saleh Atashbar, Saman Azizian, Sepideh Shaikhgermchi, Zahra Kurdpour, Peyman Salimi, Ahmad Tags: Original Article Source Type: research
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