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不同血液透析方案终末期肾病患者的基线和氧化损伤 DNA:彗星试验评估。

Baseline and oxidatively damaged DNA in end-stage renal disease patients on varied hemodialysis regimens: a comet assay assessment.

机构信息

Department of Human Genetics, Guru Nanak Dev University, Amritsar, 143001, India.

出版信息

Mol Cell Biochem. 2024 Feb;479(2):199-211. doi: 10.1007/s11010-023-04720-4. Epub 2023 Apr 1.

Abstract

Global estimates exhibit that one million people have end-stage renal disease, a disease-state characterized by irreversible loss of kidney structure and function, thus necessitating renal replacement therapy. The disease-state, oxidative stress, inflammatory responses, as well as the treatment procedure can have damaging effects on the genetic material. Therefore, the present study was carried out to investigate DNA damage (basal and oxidative) using the comet assay in peripheral blood leukocytes of patients (n = 200) with stage V Chronic Kidney Disease (on dialysis and those recommended but yet to initiate dialysis) and compare it to that in controls (n = 210). Basal DNA damage was significantly elevated (1.13x, p ≤ 0.001) in patients (46.23 ± 0.58% DNA in tail) compared to controls (40.85 ± 0.61% DNA in tail). Oxidative DNA damage was also significantly (p ≤ 0.001) higher in patients (9.18 ± 0.49 vs. 2.59 ± 0.19% tail DNA) compared to controls. Twice-a-week dialysis regimen patients had significantly elevated % tail DNA and Damage Index compared to the non-dialyzed and to the once-a-week dialysis group implying dialysis- induced mechanical stress and blood-dialyzer membrane interactions as probable contributors to elevated DNA damage. The present study with a statistically significant power implies higher disease-associated as well as maintenance therapy (hemodialysis)-induced basal and oxidatively damaged DNA, which if not repaired has the potential to initiate carcinogenesis. These findings mark the need for improvement and development of interventional therapies for delaying disease progression and associated co-morbidities so as to improve life expectancy of patients with kidney disease.

摘要

全球估计有 100 万人患有终末期肾病,这是一种以肾脏结构和功能不可逆转丧失为特征的疾病状态,因此需要肾脏替代治疗。疾病状态、氧化应激、炎症反应以及治疗过程都会对遗传物质造成损害。因此,本研究旨在使用彗星试验检测外周血白细胞中的 DNA 损伤(基础和氧化),并比较慢性肾脏病 5 期(透析和推荐但尚未开始透析)患者(n=200)和对照组(n=210)的 DNA 损伤。与对照组(尾部 DNA 为 40.85±0.61%)相比,患者的基础 DNA 损伤显著升高(1.13x,p≤0.001)(尾部 DNA 为 46.23±0.58%)。与对照组相比,患者的氧化 DNA 损伤也显著升高(p≤0.001)(尾部 DNA 为 9.18±0.49%比 2.59±0.19%)。每周两次透析方案的患者与未透析和每周一次透析组相比,尾部 DNA 和损伤指数显著升高,这表明透析引起的机械应激和血液-透析器膜相互作用可能是导致 DNA 损伤增加的原因。本研究具有统计学意义的效力表明,与疾病相关的以及维持性治疗(血液透析)引起的基础和氧化损伤 DNA 增加,如果不修复,有可能引发癌变。这些发现表明需要改进和开发干预性治疗方法,以延缓疾病进展和相关合并症,从而提高肾病患者的预期寿命。

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