Preventive effects of indole-3-carbinol against alcohol-induced liver injury in mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms: Role of gut-liver-adipose tissue axis

Indole-3-carbinol (13C), found in Brassica family vegetables, exhibits antioxidant, anti-inflammatory, and anti-cancerous properties. Here, we aimed to evaluate the preventive effects of 13C against ethanol (EtOH)-induced liver injury and study the protective mechanism(s) by using the well-established chronic plus-binge alcohol exposure model. The preventive effects of 13C were evaluated by conducting various histological, biochemical, and real-time PCR analyses in mouse liver, adipose tissue, and colon, since functional alterations of adipose tissue and intestine can also participate in promoting EtOH-induced liver damage. Daily treatment with 13C alleviated EtOH-induced liver injury and hepatocyte apoptosis, but not steatosis, by attenuating elevated oxidative stress, as evidenced by the decreased levels of hepatic lipid peroxidation, hydrogen peroxide, CYP2E1, NADPH-oxidase, and protein acetylation with maintenance of mitochondrial complex I, II, and III protein levels and activities. 13C also restored the hepatic antioxidant capacity by preventing EtOH-induced suppression of glutathione contents and mitochondrial aldehyde dehydrogenase-2 activity. 13C preventive effects were also achieved by attenuating the increased levels of hepatic proinflammatory cytokines, including IL1 beta, and neutrophil infiltration. 13C also attenuated EtOH-induced gut leakiness with decreased serum endotoxin levels through preventing EtOH-induced oxidative stress, apoptosis of enterocytes, and alteration of tight junction protein claudin-1. Furthermore, 13C alleviated adipose tissue inflammation and decreased free fatty acid release. Collectively, 13C prevented EtOH-induced liver injury via attenuating the damaging effect of ethanol on the gut-liver-adipose tissue axis. Therefore, 13C may also have a high potential for translational research in treating or preventing other types of hepatic injury associated with oxidative stress and inflammation. (C) 2017 Elsevier Inc. All rights reserved.