From bench to the hemodialysis clinic: protein-bound uremic toxins modulate NF-κB/Nrf2 expression.
Int Urol Nephrol
; 50(2): 347-354, 2018 Feb.
Article
em En
| MEDLINE
| ID: mdl-29151180
ABSTRACT
PURPOSE:
Uremic toxins produced by gut microbiota (indoxyl sulfate-IS, p-cresyl sulfate-p-CS, and indole-3-acetic acid-IAA) accumulate in hemodialysis (HD) patients and exhibit potent inflammatory effects. However, the impact of these toxins on nuclear E2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) expression in HD patients remains poorly defined. The aim of this study was to evaluate the association between uremic toxins and Nrf2/NF-κB expression in vitro (RAW 264.7 macrophage-like cells) and in peripheral blood mononuclear cells from HD patients.METHODS:
Uremic toxins, C-reactive protein (CRP), interleukin-6 (IL-6) and malondialdehyde (MDA) levels were measured in fifteen HD patients and nine healthy individuals. RAW 264.7 macrophage-like cells were incubated with IS, as a prototype of protein-bound uremic toxin. Nrf2 and NF-κB expressions were analyzed by RT-qPCR.RESULTS:
HD patients presented high levels of inflammatory markers, MDA and uremic toxins. In addition, they presented high NF-κB and low Nrf2 expression. Uremic toxins were positively correlated with NF-κB expression (IS, ρ = 0.58, p < 0.003; p-CS, ρ = 0.71, p < 0.001; IAA, ρ = 0.62, p < 0.001) and negatively with Nrf2 (IS, ρ = - 0.48, p = 0.01; p-CS, ρ = - 0.46, p < 0.02). Uremic toxins also exhibited positive correlations with CRP and MDA levels. Multivariate analysis revealed that p-CS is a determinant factor of NF-κB expression. In RAW 264.7 culture, NF-κB mRNA expression was stimulated by IS, while Nrf2 was downregulated.CONCLUSIONS:
Thus, uremic toxins may stimulate NF-κB mRNA and decrease Nrf2 expression in HD patients and, consequently, trigger inflammation and oxidative stress.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Uremia
/
NF-kappa B
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Insuficiência Renal Crônica
/
Fator 2 Relacionado a NF-E2
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
Limite:
Aged
/
Animals
/
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Int Urol Nephrol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Brasil