Role of uranium toxicity and uranium-induced oxidative stress in advancing kidney injury and endothelial inflammation in rats

作者：Yuwei Yang, Chunmei Dai, Xi Chen, Bin Zhang, Xiaohan Li, Wenyu Yang, Jun Wang, Jia-fu Feng · 发表于：BMC Pharmacology and Toxicology · 年份：2024 · DOI：10.1186/s40360-024-00734-w · 被引用次数：12 · 研究领域：Radioactivity and Radon Measurements、Selenium in Biological Systems、Mercury impact and mitigation studies

Abstract Objective Uranium exposure may cause serious pathological injury to the body, which is attributed to oxidative stress and inflammation. However, the pathogenesis of uranium toxicity has not been clarified. Here, we evaluated the level of oxidative stress to determine the relationship between uranium exposure, nephrotoxic oxidative stress, and endothelial inflammation. Methods Forty male Sprague–Dawley rats were divided into three experimental groups (U-24h, U-48h, and U-72h) and one control group. The three experimental groups were intraperitoneally injected with 2.0 mg/kg uranyl acetate, and tissue and serum samples were collected after 24, 48, and 72 h, respectively, whereas the control group was intraperitoneally injected with 1.0 ml/kg normal saline and samples were collected after 24 h. Then, we observed changes in the uranium levels and oxidative stress parameters, including the total oxidative state (TOS), total antioxidant state (TAS), and oxidative stress index (OSI) in kidney tissue and serum. We also detected the markers of kidney injury, namely urea (Ure), creatine (Cre), cystatin C (CysC), and neutrophil gelatinase-associated lipocalin (NGAL). The endothelial inflammatory markers, namely C-reactive protein (CRP), lipoprotein phospholipase A2 (Lp-PLA2), and homocysteine (Hcy), were also quantified. Finally, we analyzed the relationship among these parameters. Results TOS (z = 3.949; P < 0.001), OSI (z = 5.576; P < 0.001), Ure (z = 3.559; P < 0.00...