■无定形二氧化硅纳米颗粒(SiNPs)的利用在各种应用中越来越受欢迎,但它对人类和环境健康构成了潜在的风险。然而,SiNPs诱导的肾损伤的根本原因和机制在很大程度上仍然未知.
■本研究旨在研究SiNPs对肾脏的损伤,并进一步探讨SiNPs引起肾脏毒性的可能机制。
■将30只成年雄性大鼠分为3组。第2组和第3组的大鼠以2个剂量水平(25和100mg/kg体重)给予SiNPs,对照组大鼠28天未接受治疗。活性氧(ROS),抗氧化酶活性(谷胱甘肽过氧化物酶[GPx],超氧化物歧化酶[SOD],和过氧化氢酶[CAT]),谷胱甘肽(GSH)水平,并分析了肾脏组织中的氧化标志物(例如脂质过氧化[丙二醛(MDA)]和蛋白质氧化[蛋白质羰基(PCO)])。此外,通过组织病理学检查和纤维化生物标志物的表达水平研究了肾纤维化发生。
■这些发现揭示了用SiNP的体内治疗以剂量依赖的方式显著地触发了肾组织中的氧化应激。其特点是ROS产量增加,MDA水平升高,PCO,和一氧化氮(NO),随着SOD活性的显著下降,CAT,GPx,减少GSH。这些变化与组织病理学分析一致,这表明间质纤维化与单核炎症细胞聚集,管状变性,肾小球肾炎,和肾小球萎缩。使用Masson三色染色确认纤维化指数。此外,纤维化相关基因显著上调,包括转化生长因子-β1(TGF-β1),基质金属蛋白酶2和9(MMP-2/9),而金属蛋白酶组织抑制因子2(TIMP2)的表达下调。
■本研究为ROS和下调TGF-β信号通路在SiNPs肾毒性中的作用提供了新的研究线索。
UNASSIGNED: The utilization of amorphous silica nanoparticles (SiNPs) is gaining popularity in various applications, but it poses a potential risk to human and environmental health. However, the underlying causes and mechanisms of SiNPs-induced kidney damage are still largely unknown.
UNASSIGNED: This study aimed to investigate the SiNPs-induced damage in the kidney and further explore the possible mechanisms of SiNPs-induced nephrotoxicity.
UNASSIGNED: Thirty adult male rats were divided into 3 different groups. Rats in groups 2 and 3 were administered SiNPs at 2 dosage levels (25 and 100 mg/kg of body weight), while the rats in the control group received no treatment for 28 days. Reactive oxygen species (ROS), antioxidant enzyme activities (glutathione peroxidase [GPx], superoxide dismutase [SOD], and catalase [CAT]), glutathione (GSH) levels, and oxidation markers (such as lipid peroxidation [malondialdehyde (MDA)] and protein oxidation [protein carbonyl (PCO)]) were analyzed in the kidney tissue. Additionally, renal fibrogenesis was studied through histopathological examination and the expression levels of fibrotic biomarkers.
UNASSIGNED: The findings revealed that in vivo treatment with SiNPs significantly triggered oxidative stress in kidney tissues in a dose-dependent manner. This was characterized by increased production of ROS, elevated levels of MDA, PCO, and nitric oxide (NO), along with a significant decline in the activities of SOD, CAT, GPx, and reduced GSH. These changes were consistent with the histopathological analysis, which indicated interstitial fibrosis with mononuclear inflammatory cell aggregation, tubular degeneration, glomerulonephritis, and glomerular atrophy. The fibrosis index was confirmed using Masson\'s trichrome staining. Additionally, there was a significant upregulation of fibrosis-related genes, including transforming growth factor-beta 1 (TGF-β1), matrix metalloproteinases 2 and 9 (MMP-2/9), whereas the expression of tissue inhibitor of metalloproteinase 2 (TIMP2) was downregulated.
UNASSIGNED: This study provided a new research clue for the role of ROS and deregulated TGF-β signaling pathway in SiNPs nephrotoxicity.