title: Essential amino acid supplementation decreases liver damage induced by chronic ethanol consumption in rats.
abstract: The liver sustains the greatest damage from ethanol (EtOH) abuse. EtOH and its metabolites impair hepatocyte metabolism, causing intracellular accumulation of proteins and lipids and increasing radical oxygen species production. These processes are toxic to the mitochondrial respiratory chain and to mitochondrial DNA. We have recently shown that supplementating the diet of rodents with an essential amino acid-enriched mixture (EAAem) significantly increases mitochondrial mass and number in cardiac and skeletal muscles and improves mitochondrial function in aged animals. Thus, in this study we sought to test whether EAAem supplementation could reduce EtOH-induced liver damage. Groups of adult male Wistar rats were fed a standard diet and water ad libitum (the control group), drinking water with 20 percent EtOH (the EtOH group), or drinking water with 20 percent EtOH and EAAem supplementation (1.5 g/kg/day) (the EtOH+EAAem group) for 2 months. The blood EtOH concentration was measured, and markers for fat (Oil-Red-O), mitochondria (Grp75, Cyt-c-ox), endoplasmic reticulum (Grp78), and inflammation (Heme Oxigenase 1, iNOS, and peroxisomes) were analyzed in the liver of animals in the various experimental groups. EAAem supplementation in EtOH-drinking rats ameliorated EtOH-induced changes in liver structure by limiting steatosis, recruiting more mitochondria and peroxisomes mainly to perivenous hepatocytes, stimulating or restoring antioxidant markers, limiting the expression of inflammatory processes, and reducing ER stress. Taken together, these results suggest that EAAem supplementation may represent a promising strategy to prevent and treat EtOH-induced liver damage.
authors: Division of Human Anatomy, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy. corsetti@med.unibs.it
authors: Giovanni
authors: G
authors: Corsetti
authors: A
authors: A
authors: Stacchiotti
authors: L
authors: L
authors: Tedesco
authors: G
authors: G
authors: D'Antona
authors: E
authors: E
authors: Pasini
authors: F S
authors: FS
authors: Dioguardi
authors: E
authors: E
authors: Nisoli
authors: R
authors: R
authors: Rezzani
mesh_terms: D000428:Alcohol Drinking; D000601:Amino Acids, Essential / Q000627:therapeutic use*; D000818:Animals; D001391:Azo Compounds; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000097:blood; D004396:Coloring Agents; D019587:Dietary Supplements; D003576:Electron Transport Complex IV / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D000431:Ethanol / Q000097:blood; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism; D006519:Hepatitis, Alcoholic / Q000473:pathology* / Q000517:prevention & control*; D006651:Histocytochemistry; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008099:Liver / Q000473:pathology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000601:Amino Acids, Essential; D001391:Azo Compounds; D002492:Central Nervous System Depressants; D004396:Coloring Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D000431:Ethanol; D002374:Catalase; D003576:Electron Transport Complex IV; C011049:oil red O