Rodrigo López-Baltanás1, Maria Encarnación Rodríguez-Ortiz1,2, Antonio Canalejo3, Juan M Díaz-Tocados4,5, Carmen Herencia6, Fernando Leiva-Cepas7,8, José D Torres-Peña9,10, Ana Ortíz-Morales9,10, Juan Rafael Muñoz-Castañeda2,11, Mariano Rodríguez2,11, Yolanda Almadén10,12. 1. Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital/University of Cordoba, Córdoba, Spain. 2. Red Nacional de Investigación en Nefrología (REDinREN), Instituto de Salud Carlos III, Madrid, Spain. 3. Department of Integrated Sciences/Research Center RENSMA, University of Huelva, Huelva, Spain. 4. Biomedical Research Institute of Lleida (IRBLleida), Vascular and Renal Translational Research Group, Arnau de Vilanova University Hospital, Lleida, Spain. 5. Carlos III Health Institute (ISCIII), Madrid, Spain. 6. Renal, Vascular and Diabetes Research Laboratory, Fundación Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz,, Universidad Autónoma de Madrid, Madrid, Spain. 7. UGC de Anatomía Patología del Hospital Universitario Reina Sofía de Córdoba, Córdoba, Spain. 8. Departamento de Ciencias Morfológicas y Ciencias Sociosanitarias, Facultad de Medicina y Enfermería, Universidad de Córdoba, Córdoba, Spain. 9. Lipid and Atherosclerosis Unit, Department of Internal Medicine, IMIBIC/Reina Sofia University Hospital/University of Cordoba, Córdoba, Spain. 10. CIBER Fisiopatologia Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. 11. Instituto Maimonides de Investigacion Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital/University of Cordoba, Unidad de Gestión Clinica Nefrología, Córdoba, Spain. 12. Unidad de Gestión Clinica Medicina Interna, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital/University of Cordoba, Córdoba, Spain.
Abstract
BACKGROUND: Inflammation is a common feature in chronic kidney disease (CKD) that appears specifically associated with cardiovascular derangements in CKD patients. Observational studies have revealed a link between low Mg levels and inflammation. In this study, we hypothesize that Mg might have a modulatory effect on the inflammation induced under the uraemic milieu. METHODS: In vivo studies were performed in a 5/6 nephrectomized rat model of CKD. Furthermore, a possible direct effect of Mg was addressed through in vitro studies with vascular smooth muscle cells (VSMCs). RESULTS: Uraemic rats fed a normal (0.1%) Mg diet showed a systemic inflammatory response evidenced by the elevation in plasma of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6, and GPx activity, a marker of oxidative stress. Importantly, an increased expression of these cytokines in the aortic tissue was also observed. In contrast, a dietary Mg supplementation (0.6%) greatly prevented the oxidative stress and the pro-inflammatory response. In vitro, in VSMCs cultured in a pro-inflammatory high phosphate medium, incubation with Mg 1.6 mM inhibited the increase in the production of ROS, the rise in the expression of TNF-α, IL-1β, IL-6 and IL-8 and the activation of NF-κB signalling that was observed in cells incubated with a normal (0.8 mM) Mg. CONCLUSION: Mg supplementation reduced inflammation associated with CKD, exerting a direct effect on vascular cells. These findings support a possible beneficial effect of Mg supplementation along the clinical management of CKD patients.
BACKGROUND: Inflammation is a common feature in chronic kidney disease (CKD) that appears specifically associated with cardiovascular derangements in CKD patients. Observational studies have revealed a link between low Mg levels and inflammation. In this study, we hypothesize that Mg might have a modulatory effect on the inflammation induced under the uraemic milieu. METHODS: In vivo studies were performed in a 5/6 nephrectomized rat model of CKD. Furthermore, a possible direct effect of Mg was addressed through in vitro studies with vascular smooth muscle cells (VSMCs). RESULTS: Uraemic rats fed a normal (0.1%) Mg diet showed a systemic inflammatory response evidenced by the elevation in plasma of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6, and GPx activity, a marker of oxidative stress. Importantly, an increased expression of these cytokines in the aortic tissue was also observed. In contrast, a dietary Mg supplementation (0.6%) greatly prevented the oxidative stress and the pro-inflammatory response. In vitro, in VSMCs cultured in a pro-inflammatory high phosphate medium, incubation with Mg 1.6 mM inhibited the increase in the production of ROS, the rise in the expression of TNF-α, IL-1β, IL-6 and IL-8 and the activation of NF-κB signalling that was observed in cells incubated with a normal (0.8 mM) Mg. CONCLUSION: Mg supplementation reduced inflammation associated with CKD, exerting a direct effect on vascular cells. These findings support a possible beneficial effect of Mg supplementation along the clinical management of CKD patients.