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.

Abstract

Indole-3-carbinol (I3C), found in Brassica family vegetables, exhibits antioxidant, anti-inflammatory, and anti-cancerous properties. Here, we aimed to evaluate the preventive effects of I3C 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 I3C 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 I3C 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. I3C also restored the hepatic antioxidant capacity by preventing EtOH-induced suppression of glutathione contents and mitochondrial aldehyde dehydrogenase-2 activity. I3C preventive effects were also achieved by attenuating the increased levels of hepatic proinflammatory cytokines, including IL1β, and neutrophil infiltration. I3C 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, I3C alleviated adipose tissue inflammation and decreased free fatty acid release. Collectively, I3C prevented EtOH-induced liver injury via attenuating the damaging effect of ethanol on the gut-liver-adipose tissue axis. Therefore, I3C may also have a high potential for translational research in treating or preventing other types of hepatic injury associated with oxidative stress and inflammation.

• Authors: Youngshim Choi, Mohamed A Abdelmegeed, Byoung-Joon Song
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 55 Pg. 12-25 (05 2018) ISSN: 1873-4847 [Electronic] United States
• PMID: 29331880 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Indoles
• Ethanol
• indole-3-carbinol

Topics

• Alcoholism (pathology)
• Animals
• Antioxidants (metabolism, pharmacology)
• Apoptosis (drug effects)
• Chemical and Drug Induced Liver Injury, Chronic (metabolism, pathology, prevention & control)
• Colon (drug effects)
• Disease Models, Animal
• Ethanol (adverse effects)
• Hepatocytes (drug effects, pathology)
• Indoles (pharmacology)
• Male
• Mice, Inbred C57BL
• Neutrophils (drug effects, pathology)
• Oxidative Stress (drug effects)
• Panniculitis (pathology, prevention & control)