Genomic damage in the progression of chronic kidney disease in rats

Genomic damage in the progression of chronic kidney disease in rats

Author Hirotsu, Camila Autor UNIFESP Google Scholar
Tufik, Sergio Autor UNIFESP Google Scholar
Ribeiro, Daniel A. Autor UNIFESP Google Scholar
Alvarenga, Tathiana A. Autor UNIFESP Google Scholar
Andersen, Monica L. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
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.
Keywords Cancer
Chronic kidney disease
DNA damage
Language English
Sponsor AFIP
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: CEPID 98/14303-3
FAPESP: 07/01228-4
FAPESP: 09/010305
FAPESP: 2010/50129-1
Date 2011-03-01
Published in Brain Behavior and Immunity. San Diego: Academic Press Inc Elsevier Science, v. 25, n. 3, p. 416-422, 2011.
ISSN 0889-1591 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 416-422
Access rights Closed access
Type Article
Web of Science ID WOS:000287626600006

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