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萝卜硫素通过 Sesn2/AMPK/Nrf2 信号通路的激活来减轻六价铬诱导的心脏毒性。

Sulforaphane attenuates hexavalent chromium-induced cardiotoxicity the activation of the Sesn2/AMPK/Nrf2 signaling pathway.

机构信息

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.

出版信息

Metallomics. 2020 Dec 23;12(12):2009-2020. doi: 10.1039/d0mt00124d.

DOI:10.1039/d0mt00124d
PMID:33159781
Abstract

Hexavalent chromium (Cr(vi)), the most toxic valence state of chromium, is widely present in industrial effluents and wastes. Sulforaphane (SFN), rich in Brassica genus plants, bears multiple biological activity. Wistar rats were used to explore the protective role of SFN against the cardiotoxicity of chronic potassium dichromate (K2Cr2O7) exposure and reveal the potential molecular mechanism. The data showed that SFN alleviated hematological variations, oxidative stress, heart dysfunction and structure disorder, and cardiomyocyte apoptosis induced by K2Cr2O7. Moreover, SFN reduced p53, cleaved caspase-3, Bcl2-associated X protein, nuclear factor kappa-B, and interleukin-1β levels, and increased Sesn2, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1, NAD(P)H quinone oxidoreductase-1, and phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) levels. This study demonstrates that SFN ameliorates Cr(vi)-induced cardiotoxicity via activation of the Sesn2/AMPK/Nrf2 signaling pathway. SFN may be a protector against Cr(vi)-induced heart injury and a novel therapy for chronic Cr(vi) exposure.

摘要

六价铬(Cr(vi))是铬的毒性最大的价态,广泛存在于工业废水和废物中。富含于芸薹属植物的萝卜硫素(SFN)具有多种生物学活性。本研究采用 Wistar 大鼠来探索 SFN 对慢性重铬酸钾(K2Cr2O7)暴露引起的心脏毒性的保护作用,并揭示其潜在的分子机制。结果表明,SFN 可缓解 K2Cr2O7 引起的血液学变化、氧化应激、心脏功能障碍和结构紊乱以及心肌细胞凋亡。此外,SFN 降低了 p53、裂解的半胱氨酸天冬氨酸蛋白酶-3、Bcl2 相关 X 蛋白、核因子-κB 和白细胞介素-1β的水平,增加了Sesn2、核因子红细胞 2 相关因子 2(Nrf2)、血红素加氧酶-1、NAD(P)H 醌氧化还原酶-1 和磷酸化的腺苷 5'-单磷酸(AMP)激活的蛋白激酶(AMPK)的水平。本研究表明,SFN 通过激活 Sesn2/AMPK/Nrf2 信号通路改善 Cr(vi)诱导的心脏毒性。SFN 可能是预防 Cr(vi)诱导的心脏损伤的保护剂,也是慢性 Cr(vi)暴露的一种新型治疗方法。

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