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槲皮素和艾地苯醌对二氧化钛纳米颗粒毒性诱导的大鼠免疫炎症和氧化性肾损伤的潜在影响。

Potential impact of quercetin and idebenone against immuno- inflammatory and oxidative renal damage induced in rats by titanium dioxide nanoparticles toxicity.

作者信息

Al-Rasheed Nouf M, Faddah L M, Mohamed Azza M, Abdel Baky Nayira A, Al-Rasheed Nawal M, Mohammad Raeesa A

机构信息

Pharmacology Department, Faculty of Pharmacy, King Saud University.

出版信息

J Oleo Sci. 2013;62(11):961-71. doi: 10.5650/jos.62.961.

Abstract

The aim of this study was to investigate the toxic impacts of titanium dioxide nanoparticles (TiO₂-NPs) on rat kidneys and the possible prophylactic role of either quercetin or idebenone. TiO₂-NPs were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days to evaluate dose-dependent toxicity referred to the OECD guidelines for testing of chemicals. The results showed that administration of either low or high repeated doses of TiO₂-NPs to rats significantly increases serum kideney function biomarkers (urea, creatinine and uric acid) as well as increases in serum glucose and serum immuno- inflammatory biomarkers including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), immunoglobin g (IGg), vascular endothelial growth factor (VEGF, angiogenic factor) and nitric oxide (NO) with a concomitant decrease in renal GSH content versus normal control values. The increase in these biomarkers was more evident in rats intoxicated with high TiO₂-NPs repeated doses. Oral co- administration of either quercetin or idebenone (each 200mg/Kg body weight) daily for three weeks to rats intoxicated by either of the two doses markedly ameliorated TiO₂-NPs induced alteration in the above biomarkers. The prophylactic impacts of both agents on biochemical markers were more pronounced in rats received low TiO₂-NPs repeated doses. The biochemical investigation was supported by histological examination. In conclusion, The data showed the severity in renotoxicity of TiO₂-NPs was dose-dependent and the protective effect of quercetin and idebenone may be related to their antioxidant and anti-inflammatory properties.

摘要

本研究的目的是调查二氧化钛纳米颗粒(TiO₂-NPs)对大鼠肾脏的毒性影响以及槲皮素或艾地苯醌可能的预防作用。按照经济合作与发展组织(OECD)化学品测试指南,以600 mg或1 g/kg体重的剂量连续5天经口给予TiO₂-NPs,以评估剂量依赖性毒性。结果显示,对大鼠重复给予低剂量或高剂量的TiO₂-NPs均显著增加血清肾功能生物标志物(尿素、肌酐和尿酸),同时血清葡萄糖和血清免疫炎症生物标志物也增加,包括肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、C反应蛋白(CRP)、免疫球蛋白g(IGg)、血管内皮生长因子(VEGF,血管生成因子)和一氧化氮(NO),同时肾谷胱甘肽(GSH)含量相对于正常对照值下降。这些生物标志物的增加在高剂量TiO₂-NPs重复给药的大鼠中更为明显。对接受两种剂量之一中毒的大鼠,每天经口共同给予槲皮素或艾地苯醌(各200mg/Kg体重),持续三周,可显著改善TiO₂-NPs诱导的上述生物标志物的变化。两种药物对生化标志物的预防作用在接受低剂量TiO₂-NPs重复给药的大鼠中更为显著。生化研究得到了组织学检查的支持。总之,数据表明TiO₂-NPs肾毒性的严重程度具有剂量依赖性,槲皮素和艾地苯醌的保护作用可能与其抗氧化和抗炎特性有关。

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