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Environ Pollut. 2019 Dec 18;259:113812. doi: 10.1016/j.envpol.2019.113812. [Epub ahead of print]

Sulforaphane prevents chromium-induced lung injury in rats via activation of the Akt/GSK-3β/Fyn pathway.

Author information

1
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin, 150030, China.
2
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
3
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin, 150030, China. Electronic address: zhangzhigang@neau.edu.cn.

Abstract

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-3β) 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-3β/Fyn signaling pathway. SFN may be a novel natural substance to cure Cr-induced lung toxicity.

KEYWORDS:

Akt/GSK-3β/Fyn; Chromium; Lung toxicity; Nrf2; Sulforaphane

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