High-fat diet-induced kidney alterations in rats with metabolic syndrome: endothelial dysfunction and decreased antioxidant defense
Raquel Rangel Silvares1,*, Evelyn Nunes Goulart da Silva Pereira1,*, Edgar Eduardo Ilaquita Flores1, Karine Lino Rodrigues1, Adriana Ribeiro Silva2, Cassiano Felipe Gonçalves-de-Albuquerque2,3, Anissa Daliry1 1Laboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, Oswaldo Cru...
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2019
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| Acceso en línea: | https://doaj.org/article/605b442423bd452da7f8a6a54ce3800f |
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| Sumario: | Raquel Rangel Silvares1,*, Evelyn Nunes Goulart da Silva Pereira1,*, Edgar Eduardo Ilaquita Flores1, Karine Lino Rodrigues1, Adriana Ribeiro Silva2, Cassiano Felipe Gonçalves-de-Albuquerque2,3, Anissa Daliry1 1Laboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil; 2Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil; 3Laboratory of Immunopharmacology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, RJ, Brazil*These authors contributed equally to this workCorrespondence: Anissa DaliryInstituto Oswaldo Cruz, Fiocruz, Pavilhão Ozório de Almeida, Manguinhos, Rio de Janeiro, CEP: 21.040-360, RJ, BrazilEmail daliry@ioc.fiocruz.brIntroduction: This study aimed to investigate changes in renal function and the AGE-RAGE axis in the kidney of a non-genetic animal model of metabolic syndrome (MetS) induced by high-fat diet (HFD). Additionally, we evaluated the protective effect of pyridoxamine (PM), a vitamin B6 analog with anti-AGE effects, in the context of diet-related renal endothelial dysfunction.Methodology: In Wistar rats, the MetS animal model was induced by 20 or 28 weeks of HFD feeding. When indicated, a subgroup of animals was treated daily with PM (60 mg/kg) for 2 months. Tissue perfusion in renal microcirculation was examined by laser speckle contrast imaging. Oxidative stress was analyzed by thiobarbituric acid reactive species and the inflammatory markers by ELISA (TNF-α and IL-1β). Reverse transcription polymerase chain reaction was used to analyze eNOs, IL-6, vascular cell adhesion molecule (VCAM), NADPH oxidase subunit 47 (N47), catalase, and receptor for AGE (RAGE) gene expression.Results: Wistar rats fed a HFD showed negligible alteration in renal function, decrease in catalase mRNA transcripts and catalase enzyme activity compared to control (CTL) animals. Increased levels of IL-1β were observed in the kidney of MetS-induced rats. HFD-fed rats exhibited kidney endothelial dysfunction, with no significant differences in basal microvascular blood flow. PM significantly improved kidney vasorelaxation in HFD-fed rats. eNOS, VCAM, and RAGE gene expression and AGE content were not altered in kidneys of HFD-induced MetS rats in comparison to CTLs.Conclusions: Our findings suggest that HFD-induced microvascular dysfunction precedes the decline in renal function, and could be related to antioxidant machinery defects and inflammation activation in the kidney. PM showed a vasoprotective effect, and thus, could be an important contributory factor in ameliorating diet-induced renal damage.Keywords: metabolic syndrome, kidney endothelial dysfunction, pyridoxamine, advanced glycation end products |
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