Autor(es):
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Thieme, Karina
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Da Silva, Karolline S.
;
Fabre, Nelly T.
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Catanozi, Sergio
;
Monteiro, Maria Beatriz
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Santos-Bezerra, Daniele Pereira
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Costa-Pessoa, Juliana Martins
;
Oliveira-Souza, Maria
;
Machado, Ubiratan F.
;
Passarelli, Marisa
;
Correa-Giannella, Maria Lucia
Número total de Autores: 11
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Aim: To assess the renal effects of chronic exposure to advanced glycation end-products (AGEs) in the absence of diabetes and the potential impact of concomitant treatment with the antioxidant N-acetyl cysteine (NAC). Methods: Wistar rats received intraperitoneally 20 mg/kg/day of albumin modified (AIbAGE) or not (AIbC) by advanced glycation for 12 weeks and oral NAC (600mg/L; AIbAGE+NAC and AlbC+NAC, respectively). Biochemical, urinary and renal morphological analyses; carboxymethyl-lysine (CML, an AGE), CD68 (macrophage infiltration), and 4-hydroxynonenal (4-HNE, marker of oxidative stress) immunostaining; intrarenal mRNA expression of genes belonging to pathways related to AGEs (Ager, Ddost, Nfkb1), renin-angiotensin system (Agt, Ren, Ace), fibrosis (Tgfb1, Col4a1), oxidative stress (Nox4, Txnip), and apoptosis (Box, Bcl2); and reactive oxidative species (ROS) content were performed. Results: AIbAGE significantly increased urine protein-to-creatinine ratio; glomerular area; renal CML content and macrophage infiltration; expression of Ager, Nfkb1, Agt, Ren, Tgfb1, Col4a1, Txnip, Bax/Bcl2 ratio; and 4-HNE and ROS contents. Some of these effects were attenuated by NAC concomitant treatment. Conclusion: Because AGEs are highly consumed in modern diets and implicated in the progression of different kidney diseases, NAC could be a therapeutic intervention to decrease renal damage, considering that long-term restriction of dietary AGEs is difficult to achieve in practice. (C) 2016 The Author(s) Published by S. Karger AG, Basel (AU) |