Genomic damage in the progression of chronic kidney disease in rats

Author(s)

Hirotsu, Camila ^[1] ; Tufik, Sergio ^[1] ; Ribeiro, Daniel A. ^[2] ; Alvarenga, Tathiana A. ^[1] ; Andersen, Monica L. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Psicobiol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Biociencias, Sao Paulo - Brazil

• Document type: Journal article
• Source: BRAIN BEHAVIOR AND IMMUNITY; v. 25, n. 3, p. 416-422, MAR 2011.
• Web of Science Citations: 10

Abstract

Patients with chronic renal failure exhibit massive oxidative genome damage and an elevated risk of cancer. Previous studies have demonstrated the relationship between DNA damage and carcinogenesis. The current study aimed to investigate whether the progression of chronic kidney disease induces genomic damage in an animal model. Adult Wistar rats were assigned to either the control or chronic kidney disease groups. The chronic kidney disease group was subdistributed into five groups with progressively longer durations of disease (30, 60, 90, 120 and 150 days). The results showed that chronic kidney disease induced genomic damage in the blood, liver and kidney cells during all periods evaluated, as indicated by the mean tail moment measured in the comet assay. In brain cells, no genetic damage was induced at early/intermediate disease durations; however, positive genotoxicity was found at 120 and 150 days. Blood pressure and pro-inflammatory cytokine levels (IL-1 alpha, IL-1 beta, IL-6 and TNF alpha) were increased after chronic kidney disease induction, while blood iron concentration was significantly reduced in these animals. The results suggest that chronic kidney disease progression contributes to DNA damage in blood, liver, kidney and brain and that such damage can be mediated by hypertension, an inflammatory status and iron deficiency. Additionally, the brain was sensitive to genotoxic insult after extended chronic kidney disease, suggesting a potentially important role of genetic damage in the neurological disorders of end-stage renal patients. (C) 2010 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 07/01228-4 - Medium-term oral carcinogenesis assay induced by 4-nitroquinoline 1-oxide in rats: putative biomarkers involved into its pathogenesis
• Grantee: Daniel Araki Ribeiro
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 98/14303-3 - Center for Sleep Studies
• Grantee: Sergio Tufik
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC