Drug Res (Stuttg) 2020; 70(07): 317-324
DOI: 10.1055/a-1167-0691
Original Article

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

Saleh Khezri
1  Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
,
Saman Atashbar
1  Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
,
Sepideh Azizian
1  Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
,
Zahra Shaikhgermchi
1  Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
,
Peyman Kurdpour
1  Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
,
Ahmad Salimi
2  Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
› Author Affiliations

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.



Publication History

Received: 12 April 2020

Accepted: 27 April 2020

Publication Date:
15 May 2020 (online)

© Georg Thieme Verlag KG
Stuttgart · New York