Yüzbaşıoğlu Yücel, Hazar Merve, Aydın Dilsiz Sevtap, Yücel Ciğdem, Bulut Mesudiye, Cetinkaya Serdar, Erdem Onur, Basaran Nursen
Department of Emergency Medicine, Ankara Gülhane Training and Research Hospital, Health Sciences University, Ankara 06018, Türkiye.
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ağrı İbrahim Cecen University, Ağrı 04100, Türkiye.
Toxics. 2024 Jan 14;12(1):69. doi: 10.3390/toxics12010069.
Chronic kidney disease (CKD), a common progressive renal failure characterized by the permanent loss of functional nephrons can rapidly progress to end-stage renal disease, which is known to be an irreversible renal failure. In the therapy of ESRD, there are controversial suggestions about the use of regular dialysis, since it is claimed to increase oxidative stress, which may increase mortality in patients. In ESRD, oxidative-stress-related DNA damage is expected to occur, along with increased inflammation. Many factors, including heavy metals, have been suggested to exacerbate the damage in kidneys; therefore, it is important to reveal the relationship between these factors in ESRD patients. There are very few studies showing the role of oxidative-stress-related genotoxic events in the progression of ESRD patients. Within the scope of this study, genotoxic damage was evaluated using the comet assay and 8-OHdG measurement in patients with ESRD who were undergoing hemodialysis. The biochemical changes, the levels of heavy metals (aluminum, arsenic, cadmium, lead, and mercury) in the blood, and the oxidative biomarkers, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were evaluated, and their relationship with genotoxic damages was revealed. Genotoxicity, oxidative stress, and heavy-metal levels, except mercury, increased significantly in all renal patients. DNA damage, 8OHdG, and MDA significantly increased, and GSH significantly decreased in patients undergoing dialysis, compared with those not having dialysis. The duration and the severity of disease was positively correlated with increased aluminum levels and moderate positively correlated with increased DNA damage and cadmium levels. In conclusion, this study revealed that the oxidative-stress-related DNA damage, and also the levels of Al and Cd, increased in ESRD patients. It is assumed that these changes may play an important role in the progression of renal damage. Approaches for reducing oxidative-stress-related DNA damage and heavy-metal load in ESRD patients are recommended.
慢性肾脏病（CKD）是一种常见的进行性肾衰竭，其特征是功能性肾单位永久性丧失，可迅速进展为终末期肾病，这是一种不可逆的肾衰竭。在终末期肾病的治疗中，对于定期透析的使用存在争议性建议，因为据称它会增加氧化应激，这可能会增加患者的死亡率。在终末期肾病中，预计会发生与氧化应激相关的DNA损伤，同时炎症也会增加。许多因素，包括重金属，已被认为会加剧肾脏损伤；因此，揭示终末期肾病患者中这些因素之间的关系很重要。很少有研究表明与氧化应激相关的基因毒性事件在终末期肾病患者病情进展中的作用。在本研究范围内，使用彗星试验和8-羟基脱氧鸟苷（8-OHdG）测量法对接受血液透析的终末期肾病患者的基因毒性损伤进行了评估。评估了生化变化、血液中重金属（铝、砷、镉、铅和汞）的水平以及氧化生物标志物，包括超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和丙二醛（MDA）水平，并揭示了它们与基因毒性损伤的关系。除汞外，所有肾病患者的基因毒性、氧化应激和重金属水平均显著增加。与未接受透析的患者相比，接受透析的患者DNA损伤、8-OHdG和MDA显著增加，而谷胱甘肽（GSH）显著降低。疾病的持续时间和严重程度与铝水平升高呈正相关，与DNA损伤增加和镉水平呈中度正相关。总之，本研究表明终末期肾病患者中与氧化应激相关的DNA损伤以及铝和镉的水平增加。据推测，这些变化可能在肾损伤的进展中起重要作用。建议采取措施减少终末期肾病患者中与氧化应激相关的DNA损伤和重金属负荷。
