N-Acetyl Cysteine Attenuated the Deleterious Effects of Advanced Glycation End-Products on the Kidney of Non-Diabetic Rats

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Thieme, Karina ; Da Silva, Karolline S. ; Fabre, Nelly T. ; Catanozi, Sergio ; Monteiro, Maria Beatriz ; Santos-Bezerra, Daniele Pereira ; Costa-Pessoa, Juliana Martins ; Oliveira-Souza, Maria ; Machado, Ubiratan F. ; Passarelli, Marisa ; Correa-Giannella, Maria Lucia

• Document type: Journal article
• Source: CELLULAR PHYSIOLOGY AND BIOCHEMISTRY; v. 40, n. 3-4, p. 608-620, 2016.
• Web of Science Citations: 3

Abstract

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)

• FAPESP's process: 13/00713-7 - Effects of chronic administration of albumin modified by advanced glycation (age) on liver tissue: characterization of histological, inflammatory and antioxidant profile
• Grantee: Nelly Takashima Fabre
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/04831-1 - New players in glycemic control and chronic complications of Diabetes mellitus: preventive and therapeutic perspectives
• Grantee: Ubiratan Fabres Machado
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/17251-9 - The effects of chronic administration of albumin modified by advanced glycation (AGE) on renal tissue: characterization of the inflammatory, antioxidant and epigenetic profile
• Grantee: Karina Thieme
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/18724-2 - Advanced glycated albumin and insulin resistance in rats: focus on periepididimal adipose tissue and N-acetylcysteine actions
• Grantee: Karolline Santana da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate