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替若龙可改善二氧化钛纳米颗粒诱导雄性大鼠肾毒性中的氧化应激和炎症反应。

Tiron ameliorates oxidative stress and inflammation in titanium dioxide nanoparticles induced nephrotoxicity of male rats.

机构信息

Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

出版信息

Biomed Pharmacother. 2017 Sep;93:779-787. doi: 10.1016/j.biopha.2017.07.006. Epub 2017 Jul 12.

Abstract

Although the widespread use of titanium dioxide nanoparticles (TiO NPs), few studies were conducted on its hazard influence on human health. Tiron a synthetic vitamin E analog was proven to be a mitochondrial targeting antioxidant. The current investigation was performed to assess the efficacy of tiron against TiO NPs induced nephrotoxicity. Eighty adult male rats divided into four different groups were used: group I was the control, group II received TiO2 NPs (100mg\Kg BW), group III received TiO2 NPs plus tiron (470mg\kg BW), and group IV received tiron alone. Urea, creatinine and total protein concentrations were measured in serum to assess the renal function. Antioxidant status was estimated by determining the activities of glutathione peroxidase, superoxide dismutase, malondialdehyde (MDA) level and glutathione concentration in renal tissue. As well as Renal fibrosis was evaluated though measuring of transforming growth factor-β1 (TGFβ1) and matrix metalloproteinase 9 (MMP9) expression levels and histopathological examination. TiO NPs treated rats showed marked elevation of renal indices, depletion of renal antioxidant enzymes with marked increase in MDA concentration as well as significant up-regulation in fibrotic biomarkers TGFβ1 and MMP9. Oral administration of tiron to TiO NPs treated rats significantly attenuate the renal dysfunction through decreasing of renal indices, increasing of antioxidant enzymes activities, down-regulate the expression of fibrotic genes and improving the histopathological picture for renal tissue. In conclusion, tiron was proved to attenuate the nephrotoxicity induced by TiO NPs through its radical scavenging and metal chelating potency.

摘要

尽管二氧化钛纳米粒子(TiO NPs)被广泛应用,但对其对人类健康危害的影响研究甚少。特立诺(Tiron)是一种合成的维生素 E 类似物,已被证明是一种线粒体靶向抗氧化剂。目前的研究旨在评估特立诺对 TiO NPs 诱导的肾毒性的疗效。使用 80 只成年雄性大鼠分为四组:第 I 组为对照组,第 II 组给予 TiO2 NPs(100mg\kg BW),第 III 组给予 TiO2 NPs 加特立诺(470mg\kg BW),第 IV 组给予特立诺单独给药。通过测量血清中尿素、肌酐和总蛋白浓度来评估肾功能。通过测定肾组织中谷胱甘肽过氧化物酶、超氧化物歧化酶、丙二醛(MDA)水平和谷胱甘肽浓度来评估抗氧化状态。通过测量转化生长因子-β1(TGFβ1)和基质金属蛋白酶 9(MMP9)表达水平和组织病理学检查来评估肾纤维化。TiO NPs 处理的大鼠表现出明显的肾脏指数升高,肾脏抗氧化酶耗竭,MDA 浓度明显升高,以及纤维化生物标志物 TGFβ1 和 MMP9 的显著上调。特立诺对 TiO NPs 处理的大鼠进行口服给药可通过降低肾脏指数、增加抗氧化酶活性、下调纤维化基因的表达以及改善肾脏组织的组织病理学图像来显著减轻肾功能障碍。总之,特立诺通过其清除自由基和金属螯合能力来减轻 TiO NPs 引起的肾毒性。

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