1,25-dihydroxyvitamin D3 prevents deleterious effects of homocysteine on mitochondrial function and redox status in heart slices

• Published in: Nutrition research (New York, N.Y.) Vol. 38; pp. 52 - 63
• Main Authors: Longoni, Aline, Kolling, Janaina, Siebert, Cassiana, dos Santos, João Paulo, da Silva, Jussemara Souza, Pettenuzzo, Letícia F, Meira-Martins, Leo Anderson, Gonçalves, Carlos-Alberto, de Assis, Adriano M, Wyse, Angela TS
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-02-2017
• Subjects: Calcitriol; Energy metabolism; Gastroenterology and Hepatology; Heart slices; Homocysteine; Mitochondria function; Redox status; hyperhomocysteinemia; MTG; DMSO; dimethylsulfoxide; MTR; DA2′,7′-dihydrodichlorofluorescein diacetate; 2,4-dinitrophenylhydrazine; SDH; RNS; vitamin D receptor; energy metabolism; catalase; DCFH; Glutathione peroxidase; cytrochome c oxidase; DNPH; TBARS; 2-nitrobenzoic acid; GPx; reactive species nitrogen; TCA; MitoTracker Red CMXRos; calcitriol; superoxide dismutase; ROS; CAT; 2,6-dichloroindophenol; Hcy; trichloroacetic acid; NADPH; henazinemethosulfate; redox status; Thiobarbituric acid reactive species; Mito-Tracker Green FM; propidium iodide; reactive oxygen species; HHcy; heart slices; DTNB; VDR; 2′,7′-Dihydrodichlorofluorescein; SOD; COX; succinate dehydrogenase; mitochondria function; Nicotinamide adenine dinucleotide phosphate; PMS; DCIP; PI; Homocysteine; Energy metabolism; Calcitriol; Mitochondria function; Heart slices; Redox status
• ISSN: 0271-5317; 1879-0739
• DOI: 10.1016/j.nutres.2017.01.007

Abstract Since homocysteine (Hcy) is a risk factor for cardiovascular disease and vitamin D deficiency can contribute to cardiovascular pathologies, in the present study we tested the hypothesis that Hcy could impair energy metabolism, mitochondrial function and redox status in heart slices of Wistar rats and that 1,25-dihydroxivitamin D3 (calcitriol) treatment could prevent such effects. Heart slices were first pretreated with three different concentrations of calcitriol (50 nM, 100 nM and 250 nM) for 30 min at 37 °C, after which Hcy was added to promote deleterious effects on metabolism. After 1 h of incubation, the samples were washed, homogenized and stored at −80 °C prior to analysis. The results showed that Hcy caused changes in energy metabolism (respiratory chain enzymes), mitochondrial function, and cell viability. Hcy also induced oxidative stress, increasing lipid peroxidation, reactive oxygen species (ROS) generation, and protein damage. An imbalance in antioxidant enzymes was also observed. Calcitriol (50 nM) reverted the effect of Hcy on the parameters tested, except for the immunocontent of catalase (CAT). Both treatments (calcitriol and Hcy) did not alter the vitamin D receptor (VDR) immunocontent, which combined with the fact that our ex vivo model is acute, suggested that the beneficial effect of calcitriol occurs directly through antioxidative mechanisms and not via gene expression. In this study, we show that Hcy impairs mitochondrial function and induces changes in the redox status in heart slices, which were reverted by calcitriol. These findings suggest that calcitriol may be a preventive/therapeutic strategy for complications caused by Hcy.