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Alcoholism is a well-known risk factor for liver injury and is one of the major causes of hepatic steatosis worldwide. Although many drugs have been reported to have protective effects against acute alcohol-induced hepatotoxicity, there is limited available treatment for alcoholic liver disease (ALD), indicating an urgent need for effective therapeutic options. Herein, we first reported the protective effects of magnesium isoglycyrrhizinate (MgIG) on acute alcohol-induced hepatic steatosis and its related mechanisms in a zebrafish mode