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

被引:6
作者
Khezri, Saleh [1 ]
Atashbar, Saman [1 ]
Azizian, Sepideh
Shaikhgermchi, Zahra [1 ]
Kurdpour, Peyman [1 ]
Salimi, Ahmad [2 ]
机构
[1] Ardabil Univ Med Sci, Fac Pharm, Students Res Comm, Ardebil, Iran
[2] Ardabil Univ Med Sci, Sch Pharm, Dept Pharmacol & Toxicol, Ardebil, Iran
关键词
diclofenac; calcitriol; vitamin D; mitochondria; cardiotoxicity; SERUM 25-HYDROXYVITAMIN D; VITAMIN-D; MYOCARDIAL-INFARCTION; RISK; SUPPLEMENTATION; VIVO;
D O I
10.1055/a-1167-0691
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 mu M) for 5 min at 37 degrees C, after which DIC (10 mu g/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 mu g/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 mu M) 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.
引用
收藏
页码:317 / 324
页数:8
相关论文
共 35 条
[1]  
Al Maruf A, 2018, METHOTREXATE INDUCED, V41, P151
[2]   INHIBITION OF LIPID-PEROXIDATION PROMOTED BY IRON(III) AND ASCORBATE [J].
BEACH, DC ;
GIROUX, E .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1992, 297 (02) :258-264
[3]  
Bouillon R, 2013, VITAMIN D MITOCHONDR
[4]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[5]   The potential regulatory role of vitamin D in the bioenergetics of inflammation [J].
Calton, Emily K. ;
Keane, Kevin N. ;
Soares, Mario J. .
CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE, 2015, 18 (04) :367-373
[6]   Megalin and cubilin: Multifunctional endocytic receptors [J].
Christensen, EI ;
Birn, H .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2002, 3 (04) :258-268A
[7]   The Vitamin D Receptor Inhibits the Respiratory Chain, Contributing to the Metabolic Switch that Is Essential for Cancer Cell Proliferation [J].
Consiglio, Marco ;
Destefanis, Michele ;
Morena, Deborah ;
Foglizzo, Valentina ;
Forneris, Mattia ;
Pescarmona, Gianpiero ;
Silvagno, Francesca .
PLOS ONE, 2014, 9 (12)
[8]   Cardioprotective effect of vitamin D2 on isoproterenol-induced myocardial infarction in diabetic rats* [J].
El Agaty, Sahar M. .
ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY, 2019, 125 (03) :210-219
[9]   Mitochondria-targeted ROS scavenger improves post-ischemic recovery of cardiac function and attenuates mitochondrial abnormalities in aged rats [J].
Escobales, Nelson ;
Nunez, Rebeca E. ;
Jang, Sehwan ;
Parodi-Rullan, Rebecca ;
Ayala-Pena, Sylvette ;
Sacher, Joshua R. ;
Skoda, Erin M. ;
Wipf, Peter ;
Frontera, Walter ;
Javadov, Sabzali .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2014, 77 :136-146
[10]   Plasma 25-hydroxyvitamin D levels and risk of incident hypertension [J].
Forman, John P. ;
Giovannucci, Edward ;
Holmes, Michelle D. ;
Bischoff-Ferrari, Heike A. ;
Tworoger, Shelley S. ;
Willett, Walter C. ;
Curhan, Gary C. .
HYPERTENSION, 2007, 49 (05) :1063-1069