Aged Garlic Extract Prevents Alcohol‐Induced Cytotoxicity through Induction of Aldehyde Dehydrogenase 2 in the Liver of Mice

Abstract

ScopeAcetaldehyde is a highly toxic primary metabolite of ethanol, and converts to nontoxic acetic acid by aldehyde dehydrogenase (ALDH). Accumulation of acetaldehyde causes significant damage to human body. Aged garlic extract (AGE) is a functional food material and possesses various health beneficial effects. This study investigates whether AGE contributes to acetaldehyde detoxification through ALDH induction and its underlying mechanism.Methods and resultsC57BL/6J mice are orally administrated 10–1000 mg kg−1 body weight (BW) of AGE for 1 week before ethanol administration. AGE suppresses ethanol‐caused accumulation of acetaldehyde level in the plasma through inducing mitochondrial ALDH2 but not cytosolic ALDH1A1. AGE also induces antioxidant enzymes, heme oxygenase‐1, and NAD(P)H:quinone oxidoreductase 1, resulting in prevention of lipid peroxidation in the liver. In HepG2 cells, AGE prevents ethanol‐ and acetaldehyde‐caused cytotoxicity. AGE induces mitochondrial ALDH2 through activating nuclear factor‐erythroid 2‐related factor 2 (Nrf2). AGE inhibits protein degradation of Nrf2 and enhances protein degradation of kelch‐like ECH‐associated protein 1. Furthermore, S‐allyl cysteine and S‐allyl mercaptocysteine as the bioactive compounds in AGE also induce ALDH2 and Nrf2.ConclusionAGE prevents acetaldehyde‐induced hepatotoxicity through enhancing acetaldehyde detoxification through Nrf2‐dependent induction of mitochondrial ALDH2.