Departamento de Psicobiologia, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil.
Brain Behav Immun. 2011 Mar;25(3):416-22. doi: 10.1016/j.bbi.2010.10.021. Epub 2010 Oct 23.
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-1α, IL-1β, IL-6 and TNFα) 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.
慢性肾衰竭患者表现出大量氧化基因组损伤和癌症风险增加。先前的研究已经证明了 DNA 损伤与致癌作用之间的关系。本研究旨在探讨慢性肾脏病的进展是否会在动物模型中引起基因组损伤。成年 Wistar 大鼠被分为对照组和慢性肾脏病组。慢性肾脏病组进一步分为五个亚组，疾病持续时间逐渐延长（30、60、90、120 和 150 天）。结果表明，在所有评估的时期，慢性肾脏病都会在血液、肝脏和肾脏细胞中引起基因组损伤，这一点可以通过彗星试验测量的平均尾部矩来表明。在脑细胞中，在早期/中期疾病持续时间内没有诱导遗传损伤；然而，在 120 和 150 天时发现了阳性遗传毒性。慢性肾脏病诱导后，血压和促炎细胞因子水平（IL-1α、IL-1β、IL-6 和 TNFα）升高，而这些动物的血液铁浓度显著降低。结果表明，慢性肾脏病的进展会导致血液、肝脏、肾脏和大脑中的 DNA 损伤，这种损伤可能是由高血压、炎症状态和缺铁引起的。此外，在慢性肾脏病持续时间延长后，大脑对遗传毒性物质敏感，这表明遗传损伤在终末期肾病患者的神经紊乱中可能具有重要作用。
