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Toxicol In Vitro. 2019 Jun;57:226-232. doi: 10.1016/j.tiv.2019.03.008. Epub 2019 Mar 7.

Gallic acid protects against ethanol-induced hepatocyte necroptosis via an NRF2-dependent mechanism.

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School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
Department of Pharmacology, School of Pharmacy, Wannan Medical College, Wuhu, Anhui, China.
Department of Pharmacy, Nantong Hospital of Traditional Chinese Medicine, Nantong, Jiangsu, China.
School of Pharmacy, Nantong University, Nantong, Jiangsu, China. Electronic address:
School of Pharmacy, Nantong University, Nantong, Jiangsu, China; Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China. Electronic address:


Alcoholic liver disease (ALD), featured by excessive hepatocyte death and inflammation, is a prevalent disease that causes heavy health burdens worldwide. Hepatocyte necroptosis is a central event that promotes inflammation in ALD. At molecular levels, inhibition of nuclear factor (erythroid - derived 2) - like 2 (NRF2) was an important trigger for cell necroptosis. The protective effects of gallic acid (GA) on liver diseases caused by multiple factors have been elucidated, however, the role of GA in ALD remained unclear. Therefore, this study was aimed to investigate the anti-ALD effects of GA and further reveal the molecular mechanisms. Results showed that GA could effectively recover cell viability and reduce the release of aspartate transaminase, alanine transaminase, and lactic dehydrogenase by ethanol-stimulated hepatocytes. More importantly, GA limited hepatocyte necroptosis under ethanol stimulation, which was characterized by reduced expression of distinct necroptotic signals receptor-interacting protein 1 (RIP1) and RIP3 and release of high mobility group box protein 1. Mechanistically, GA could induce NRF2 expression in ethanol-incubated hepatocytes, which was a molecular basis for GA to suppress ethanol-induced hepatocyte necroptosis. In conclusion, this study demonstrated that GA improved ethanol-induced hepatocyte necroptosis in vitro. Further, NRF2 activation might be requisite for GA to exert its protective effects.


Ethanol; Gallic acid; Hepatocyte; NRF2; Necroptosis

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