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N-乙酰半胱氨酸和维生素 E 对双酚 A 诱导的大鼠肾毒性的肾保护作用;Nrf2/NF-κB 和 ROS 信号通路的调节剂。

Renoprotective effect of N-acetylcystein and vitamin E in bisphenol A-induced rat nephrotoxicity; Modulators of Nrf2/ NF-κB and ROS signaling pathway.

机构信息

Lecturer in Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine Mansoura University, Egypt.

2- Lecturer in Anatomy and Embrology Department, Faculty of Medicine Mansoura University, Egypt..

出版信息

Acta Biomed. 2022 Dec 16;93(6):e2022301. doi: 10.23750/abm.v93i6.13732.

Abstract

BACKGROUND AND AIM OF THE WORK

Bisphenol A (BPA) is a chemical product that is widely used as a plastic precursor. It acts directly on the kidney mitochondria, causing renal dysfunction. N-acetylcysteine is effective in protecting the kidneys from chemical-induced damage. Vitamin E is an antioxidant that protects cells from the damaging effects of free radicals. The aim of this study is to further evaluate and compare NAC and vitamin E to oppose the nephrotoxicity caused by BPA.

RESEARCH DESIGN AND METHODS

Forty-two adult male rats were divided into 7 groups:  control, BPA, NAC, vitamin E, BPA plus NAC, BPA plus vitamin E, and combined BPA, NAC and vitamin E. BPA, NAC, vitamin E were given orally at doses of 50 mg/kg, 200 mg/kg, and 1000 mg/kg respectively, for 5 weeks.

RESULTS

NAC and vitamin E groups showed improved kidney function tests and alleviated BPA-induced oxidative stress; increased GSH and decreased MDA, NO and iNOS levels. NAC and vitamin E significantly attenuated inflammation; decreased NF-κB and increased IL-4, and Nrf2, in addition there was alleviation of renal histopathology. To some extent, vitamin E administration showed significant improvement. Moreover, combined NAC and vitamin E treatment showed more significance than either NAC or vitamin E separate groups.

CONCLUSIONS

This study determined the substantial protective effects of NAC and/or vitamin E in BPA-induced nephrotoxicity through modulation of Nrf2 with subsequent improvement of oxidative stress and inflammation. The alleviation was more significant in combined NAC and vitamin E treatment mainly through their synergistic effect on Nrf2.

摘要

背景与目的

双酚 A(BPA)是一种广泛用作塑料前体的化学物质。它直接作用于肾脏线粒体,导致肾功能障碍。N-乙酰半胱氨酸(NAC)在保护肾脏免受化学诱导损伤方面有效。维生素 E 是一种抗氧化剂,可保护细胞免受自由基的破坏作用。本研究旨在进一步评估和比较 NAC 和维生素 E 以抵抗 BPA 引起的肾毒性。

研究设计与方法

将 42 只成年雄性大鼠分为 7 组:对照组、BPA 组、NAC 组、维生素 E 组、BPA+NAC 组、BPA+维生素 E 组和联合 BPA、NAC 和维生素 E 组。BPA、NAC 和维生素 E 分别以 50mg/kg、200mg/kg 和 1000mg/kg 的剂量口服给予,持续 5 周。

结果

NAC 和维生素 E 组的肾功能试验得到改善,缓解了 BPA 诱导的氧化应激;增加了 GSH,降低了 MDA、NO 和 iNOS 水平。NAC 和维生素 E 显著减轻了炎症;降低了 NF-κB,增加了 IL-4 和 Nrf2,此外还缓解了肾脏组织病理学。维生素 E 给药在某种程度上显示出显著改善。此外,联合 NAC 和维生素 E 治疗比单独使用 NAC 或维生素 E 组更有意义。

结论

本研究通过调节 Nrf2 确定了 NAC 和/或维生素 E 在 BPA 诱导的肾毒性中的实质性保护作用,随后改善了氧化应激和炎症。联合 NAC 和维生素 E 治疗的缓解作用更为显著,主要是通过它们对 Nrf2 的协同作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4c3/9828897/9023b422c8d1/ACTA-93-301-g001.jpg

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