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Oleocanthal supplemented diet improves renal damage and endothelial dysfunction in pristane-induced systemic lupus erythematosus in mice

Authors

Montoya, Tatiana , Sanchez-Hidalgo, Marina , CASTEJÓN MARTÍNEZ, MARÍA LUISA, Victoria Vazquez-Roman, Maria , Alvarez de Sotomayor, Maria , Ortega-Vidal, Juan , Luisa Gonzalez, Maria , Alarcon-de-la-Lastra, Catalina

External publication

No

Means

Food Res. Int.

Scope

Article

Nature

Científica

JCR Quartile

1

SJR Quartile

1

JCR Impact

7

SJR Impact

1.495

Publication date

01/01/2023

ISI

000896881200001

Abstract

Systemic lupus erythematosus (SLE) is a multiorgan disorder with a deregulated immune-inflammatory response. Nutritional therapy has been considered a promising approach to SLE management. Oleocanthal (OLE), the main extra virgin olive oil (EVOO)-derived secoiridoid, has shown to regulate the immune-inflammatory response in various disease contexts; however, its possible beneficial effects on SLE remain unclear. This study sought to evaluate the effects of OLE enriched diet on renal damage and aortic endothelial dysfunction in murine pristaneinduced SLE, focusing on the action mechanisms and signaling pathways involved. BALB/c mice were injected with pristane and fed with OLE supplemented diet (0.01 % (w/w)) for six months. Levels of cytokines were measured by ELISA in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and splenocytes. Presence of immunoglobulin G (IgG) and IgM immune complexes were examined by immunofluorescence and immunohistochemistry. Thoracic aortas were used to evaluate endothelial dysfunction. Western blotting was employed to detect signaling pathways and oxidative-inflammatory-related mediators. Dietary OLE supplementation reduced Th1/Th17 pro-inflammatory cytokines production and alleviated renal damage by decreasing immunoglobulin complexes deposition, and inflammation-mediating enzymes expression. The mechanisms underlying these protective effects could be related to the regulation of nuclear factor erythroid 2-related factor 2/Haem oxygenase 1 (Nrf-2/HO-1), mitogen-activated protein kinases (MAPKs), signal transducer and transcription activator of transcription (STAT-3), inflammasome and, nuclear factor kappa B (NF-kappa B) signaling pathways. Also, dietary OLE improved aortic endothelial dysfunction and vascular reactivity, normalizing endothelial nitric oxide synthase (eNOS) uncoupling, and NADPH oxidase-1 (NOX-1) overexpression. This study shows the immunomodulatory effects of OLE in an in vivo model of SLE by improving renal damage and regulating aortic endothelial dysfunction. These preliminary results provide OLE as a new therapeutic strategy in SLE management.

Keywords

Extra virgin olive oil; Immunomodulation; Lupus nephritis; Nutritional therapy; Secoiridoid; SLE; Vascular reactivity

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