Sulforaphane prevents chromium-induced lung injury in rats via activation of the Akt/GSK-3β/Fyn pathway
Sulforaphane prevents chromium-induced lung injury in rats via activation of the Akt/GSK-3β/Fyn pathway
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DOI：
10.1016/j.envpol.2019.113812
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发表时间：
2020-04-01
影响因子：
8.9
通讯作者：
Zhang, Zhigang
中科院分区：
文献类型：
--
作者：
Lv, Yueying;Jiang, Huijie;Zhang, Zhigang
铬是一种国际公认的致癌危险物质，可引起严重的肺部毒性。然而，迄今为止，铬所致的肺毒性缺乏有效的治疗方法。萝卜硫醚(SFN)是一种著名的有机硫化合物，因其独特的生物学功能而受到越来越多的关注。本研究采用大鼠35天铬中毒模型和小鼠肺泡II型上皮细胞系(MLE-12)，研究三七总皂甙能否减轻K2Cr2O7所致的肺毒性及其可能的机制。结果表明，SFN在体内和体外均能预防铬诱导的氧化应激、组织病理损伤、炎症反应、细胞凋亡以及蛋白激酶B(Akt)和糖原合成酶3β(GSK-3β)水平的变化。但经Akt特异性抑制剂MK-2206 2HCl处理后，SFN不能对K2Cr2O7诱导的细胞损伤起到保护作用。此外，SFN还增加了核因子-E2相关因子-2(Nrf2)II期解毒酶的表达。总之，本研究表明，SFN通过激活Akt/GSK-3β/Fyn信号通路，增强Nrf2介导的外源性抗氧化防御，从而预防K2Cr2O7诱导的大鼠肺毒性。SFN可能是治疗铬肺毒性的一种新的天然物质。(C)2019爱思唯尔有限公司。保留所有权利。
Chromium (Cr) is an internationally recognized carcinogenic hazard that causes serious pulmonary toxicity. However, Cr-induced pulmonary toxicity lacks effective treatment to date. Sulforaphane (SFN), a well-known organosulfur compound, has gained increasing attention because of its unique biological function. This study investigates if SFN could decrease K2Cr2O7-induced pulmonary toxicity and a potential mechanism involved using a rat 35-day Cr-induced pulmonary toxicity model and the mouse alveolar type II epithelial cell line (MLE-12). The results showed that SFN prevented Cr-induced oxidative stress, histopathological lesions, inflammation, apoptosis, and changes in protein kinase B (Akt) and glycogen synthase kinase 3 beta (GSK-3 beta) levels in vivo and in vitro. However, SFN can not play the protective effect against K2Cr2O7-induced cell injury after treating by an Akt-specific inhibitor (MK-2206 2HCl) in MLE-12 cells. Furthermore, SFN increased the expression of nuclear factor-E2-related factor-2 (Nrf2) phase II detoxification enzymes. Collectively, this study demonstrates that SFN prevents K2Cr2O7-induced lung toxicity in rats through enhancing Nrf2-mediated exogenous antioxidant defenses via activation of the Akt/GSK-3 beta/Fyn signaling pathway. SFN may be a novel natural substance to cure Cr-induced lung toxicity. (C) 2019 Elsevier Ltd. All rights reserved.