Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice

Systemic lupus erythematosus (SLE) is a chronic immune-inflammatory disease characterized by multiorgan affectation and lowered self-tolerance. Additionally, epigenetic changes have been described as playing a pivotal role in SLE. This work aims to assess the effects of oleacein (OLA), one of the ma...

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Main Authors: Rocío Muñoz-García, Marina Sánchez-Hidalgo, Manuel Alcarranza, María Victoria Vazquéz-Román, María Alvarez de Sotomayor, María Luisa González-Rodríguez, María C. de Andrés, Catalina Alarcón-de-la-Lastra
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/12/6/1303
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author Rocío Muñoz-García
Marina Sánchez-Hidalgo
Manuel Alcarranza
María Victoria Vazquéz-Román
María Alvarez de Sotomayor
María Luisa González-Rodríguez
María C. de Andrés
Catalina Alarcón-de-la-Lastra
author_facet Rocío Muñoz-García
Marina Sánchez-Hidalgo
Manuel Alcarranza
María Victoria Vazquéz-Román
María Alvarez de Sotomayor
María Luisa González-Rodríguez
María C. de Andrés
Catalina Alarcón-de-la-Lastra
author_sort Rocío Muñoz-García
collection DOAJ
description Systemic lupus erythematosus (SLE) is a chronic immune-inflammatory disease characterized by multiorgan affectation and lowered self-tolerance. Additionally, epigenetic changes have been described as playing a pivotal role in SLE. This work aims to assess the effects of oleacein (OLA), one of the main extra virgin olive oil secoiridoids, when used to supplement the diet of a murine pristane-induced SLE model. In the study, 12-week-old female BALB/c mice were injected with pristane and fed with an OLA-enriched diet (0.01 % (<i>w</i>/<i>w</i>)) for 24 weeks. The presence of immune complexes was evaluated by immunohistochemistry and immunofluorescence. Endothelial dysfunction was studied in thoracic aortas. Signaling pathways and oxidative-inflammatory-related mediators were evaluated by Western blotting. Moreover, we studied epigenetic changes such as DNA methyltransferase (DNMT-1) and micro(mi)RNAs expression in renal tissue. Nutritional treatment with OLA reduced the deposition of immune complexes, ameliorating kidney damage. These protective effects could be related to the modulation of mitogen-activated protein kinases, the Janus kinase/signal transducer and transcription activator of transcription, nuclear factor kappa, nuclear-factor-erythroid-2-related factor 2, inflammasome signaling pathways, and the regulation of miRNAs (miRNA-126, miRNA-146a, miRNA-24-3p, and miRNA-123) and DNMT-1 expression. Moreover, the OLA-enriched diet normalized endothelial nitric oxide synthase and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1 overexpression. These preliminary results suggest that an OLA-supplemented diet could constitute a new alternative nutraceutical therapy in the management of SLE, supporting this compound as a novel epigenetic modulator of the immunoinflammatory response.
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spelling doaj.art-772efe85311c4aef8c8b503ea32a3fc82023-11-18T09:04:19ZengMDPI AGAntioxidants2076-39212023-06-01126130310.3390/antiox12061303Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced MiceRocío Muñoz-García0Marina Sánchez-Hidalgo1Manuel Alcarranza2María Victoria Vazquéz-Román3María Alvarez de Sotomayor4María Luisa González-Rodríguez5María C. de Andrés6Catalina Alarcón-de-la-Lastra7Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Seville, SpainDepartment of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Seville, SpainDepartment of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Seville, SpainDepartment of Normal and Pathological Cytology and Histology, Faculty of Medicine, Universidad de Sevilla, 41012 Seville, SpainDepartment of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Seville, SpainDepartment of Pharmaceutical Technology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Seville, SpainUnidad de Epigenética, Grupo de Investigación en Reumatología (GIR), Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario, de A Coruña (CHUAC), Sergas, 15006 A Coruña, SpainDepartment of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Seville, SpainSystemic lupus erythematosus (SLE) is a chronic immune-inflammatory disease characterized by multiorgan affectation and lowered self-tolerance. Additionally, epigenetic changes have been described as playing a pivotal role in SLE. This work aims to assess the effects of oleacein (OLA), one of the main extra virgin olive oil secoiridoids, when used to supplement the diet of a murine pristane-induced SLE model. In the study, 12-week-old female BALB/c mice were injected with pristane and fed with an OLA-enriched diet (0.01 % (<i>w</i>/<i>w</i>)) for 24 weeks. The presence of immune complexes was evaluated by immunohistochemistry and immunofluorescence. Endothelial dysfunction was studied in thoracic aortas. Signaling pathways and oxidative-inflammatory-related mediators were evaluated by Western blotting. Moreover, we studied epigenetic changes such as DNA methyltransferase (DNMT-1) and micro(mi)RNAs expression in renal tissue. Nutritional treatment with OLA reduced the deposition of immune complexes, ameliorating kidney damage. These protective effects could be related to the modulation of mitogen-activated protein kinases, the Janus kinase/signal transducer and transcription activator of transcription, nuclear factor kappa, nuclear-factor-erythroid-2-related factor 2, inflammasome signaling pathways, and the regulation of miRNAs (miRNA-126, miRNA-146a, miRNA-24-3p, and miRNA-123) and DNMT-1 expression. Moreover, the OLA-enriched diet normalized endothelial nitric oxide synthase and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1 overexpression. These preliminary results suggest that an OLA-supplemented diet could constitute a new alternative nutraceutical therapy in the management of SLE, supporting this compound as a novel epigenetic modulator of the immunoinflammatory response.https://www.mdpi.com/2076-3921/12/6/1303endothelial dysfunctionepigeneticimmunomodulationlupus nephritismiRNAsnutritional therapy
spellingShingle Rocío Muñoz-García
Marina Sánchez-Hidalgo
Manuel Alcarranza
María Victoria Vazquéz-Román
María Alvarez de Sotomayor
María Luisa González-Rodríguez
María C. de Andrés
Catalina Alarcón-de-la-Lastra
Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice
Antioxidants
endothelial dysfunction
epigenetic
immunomodulation
lupus nephritis
miRNAs
nutritional therapy
title Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice
title_full Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice
title_fullStr Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice
title_full_unstemmed Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice
title_short Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice
title_sort effects of dietary oleacein treatment on endothelial dysfunction and lupus nephritis in balb c pristane induced mice
topic endothelial dysfunction
epigenetic
immunomodulation
lupus nephritis
miRNAs
nutritional therapy
url https://www.mdpi.com/2076-3921/12/6/1303
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