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大鼠亚慢性腹腔注射暴露于元素氧化物纳米颗粒后的肾毒性损伤

Toxic Kidney Damage in Rats Following Subchronic Intraperitoneal Exposure to Element Oxide Nanoparticles.

作者信息

Ryabova Yuliya V, Minigalieva Ilzira A, Sutunkova Marina P, Klinova Svetlana V, Tsaplina Alexandra K, Valamina Irene E, Petrunina Ekaterina M, Tsatsakis Aristides M, Mamoulakis Charalampos, Stylianou Kostas, Kuzmin Sergey V, Privalova Larisa I, Katsnelson Boris A

机构信息

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 620014 Yekaterinburg, Russia.

Department of Pathology, Ural State Medical University, 620028 Yekaterinburg, Russia.

出版信息

Toxics. 2023 Sep 19;11(9):791. doi: 10.3390/toxics11090791.

Abstract

Chronic diseases of the urogenital tract, such as bladder cancer, prostate cancer, reproductive disorders, and nephropathies, can develop under the effects of chemical hazards in the working environment. In this respect, nanosized particles generated as by-products in many industrial processes seem to be particularly dangerous to organs such as the testes and the kidneys. Nephrotoxicity of element oxide particles has been studied in animal experiments with repeated intraperitoneal injections of AlO, TiO, SiO, PbO, CdO, CuO, and SeO nanoparticles (NPs) in total doses ranging from 4.5 to 45 mg/kg body weight of rats. NPs were synthesized by laser ablation. After cessation of exposure, we measured kidney weight and analyzed selected biochemical parameters in blood and urine, characterizing the state of the excretory system. We also examined histological sections of kidneys and estimated proportions of different cells in imprint smears of this organ. All element oxide NPs under investigation demonstrated a nephrotoxic effect following subchronic exposure. Following the exposure to SeO and SiO NPs, we observed a decrease in serum creatinine and urea, respectively. Exposure to AlO NPs caused an increase in urinary creatinine and urea, while changes in total protein were controversial, as it increased under the effect of AlO NPs and was reduced after exposure to CuO NPs. Histomorphological changes in kidneys are associated with desquamation of the epithelium (following the exposure to all NPs except those of AlO and SiO) and loss of the brush border (following the exposure to all NPs, except those of AlO, TiO, and SiO). The cytomorphological evaluation showed greater destruction of proximal sections of renal tubules. Compared to the controls, we observed statistically significant alterations in 42.1% (8 of 19) of parameters following the exposure to PbO, CuO, and SeO NPs in 21.1% (4 of 19)-following that, to CdO and AlO NPs-and in 15.8% (3 of 19) and 10.5% (2 of 19) of indicators, following the exposure to TiO and SiO nanoparticles, respectively. Histomorphological changes in kidneys are associated with desquamation of epithelium and loss of the brush border. The cytomorphological evaluation showed greater destruction of proximal sections of renal tubules. The severity of cyto- and histological structural changes in kidneys depends on the chemical nature of NPs. These alterations are not always consistent with biochemical ones, thus impeding early clinical diagnosis of renal damage. Unambiguous ranking of the NPs examined by the degree of their nephrotoxicity is difficult. Additional studies are necessary to establish key indicators of the nephrotoxic effect, which can facilitate early diagnosis of occupational and nonoccupational nephropathies.

摘要

泌尿生殖道的慢性疾病,如膀胱癌、前列腺癌、生殖系统疾病和肾病,可能在工作环境中的化学危害影响下发生。在这方面,许多工业过程中作为副产品产生的纳米颗粒似乎对睾丸和肾脏等器官特别危险。通过对大鼠进行腹腔内重复注射总剂量为4.5至45毫克/千克体重的氧化铝、二氧化钛、二氧化硅、氧化铅、氧化镉、氧化铜和氧化硒纳米颗粒(NPs)的动物实验,研究了元素氧化物颗粒的肾毒性。纳米颗粒通过激光烧蚀合成。停止暴露后,我们测量了肾脏重量,并分析了血液和尿液中的选定生化参数,以表征排泄系统的状态。我们还检查了肾脏的组织切片,并估计了该器官印片涂片中不同细胞的比例。所有研究的元素氧化物纳米颗粒在亚慢性暴露后均表现出肾毒性作用。暴露于氧化硒和二氧化硅纳米颗粒后,我们分别观察到血清肌酐和尿素的降低。暴露于氧化铝纳米颗粒导致尿肌酐和尿素增加,而总蛋白的变化存在争议,因为在氧化铝纳米颗粒的作用下总蛋白增加,而在暴露于氧化铜纳米颗粒后总蛋白降低。肾脏的组织形态学变化与上皮细胞脱落(暴露于除氧化铝和二氧化硅之外的所有纳米颗粒后)和刷状缘丧失(暴露于除氧化铝、二氧化钛和二氧化硅之外的所有纳米颗粒后)有关。细胞形态学评估显示肾小管近端部分的破坏更大。与对照组相比,我们观察到在暴露于氧化铅、氧化铜和氧化硒纳米颗粒后,42.1%(19个中的8个)的参数有统计学显著变化;在暴露于氧化镉和氧化铝纳米颗粒后,21.1%(19个中的4个)的参数有统计学显著变化;在暴露于二氧化钛和二氧化硅纳米颗粒后,分别有15.8%(19个中的3个)和10.5%(19个中的2个)的指标有统计学显著变化。肾脏的组织形态学变化与上皮细胞脱落和刷状缘丧失有关。细胞形态学评估显示肾小管近端部分的破坏更大。肾脏细胞和组织结构变化的严重程度取决于纳米颗粒的化学性质。这些变化并不总是与生化变化一致,从而妨碍了肾脏损伤的早期临床诊断。按肾毒性程度对所研究的纳米颗粒进行明确排序很困难。需要进行更多研究以确定肾毒性作用的关键指标,这有助于早期诊断职业性和非职业性肾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddea/10537166/ab272f128c2a/toxics-11-00791-g001.jpg

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