title: Dietary tomato powder inhibits alcohol-induced hepatic injury by suppressing cytochrome p450 2E1 induction in rodent models.
abstract: Chronic and excessive alcohol consumption leads to the development of alcoholic liver disease (ALD) and greatly increases the risk of liver cancer. Induction of the cytochrome p450 2E1 (CYP2E1) enzyme by chronic and excessive alcohol intake is known to play a role in the pathogenesis of ALD. High intake of tomatoes, rich in the carotenoid lycopene, is associated with a decreased risk of chronic disease. We investigated the effects of whole tomato (tomato powder, TP), partial tomato (tomato extract, TE), and purified lycopene (LYC) against ALD development in rats. Of the three supplements, only TP reduced the severity of alcohol-induced steatosis, hepatic inflammatory foci, and CYP2E1 protein levels. TE had no effect on these outcomes and LYC greatly increased inflammatory foci in alcohol-fed rats. To further support the protective effect of TP against ALD, TP was supplemented in a carcinogen (diethylnitrosamine, DEN)-initiated alcohol-promoted mouse model. In addition to reduced steatosis and inflammatory foci, TP abolished the presence of preneoplastic foci of altered hepatocytes in DEN-injected mice fed alcohol. These reductions were associated with decreased hepatic CYP2E1 protein levels, restored levels of peroxisome proliferator-activated receptor-α and downstream gene expression, decreased inflammatory gene expression, and reduced endoplasmic reticulum stress markers. These data provide strong evidence for TP as an effective whole food prevention strategy against ALD.
authors.affiliation: Nutrition and Cancer Biology Laboratory, Jean-Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.
authors.forename: Camilla P
authors.initials: CP
authors.lastname: Stice
authors.affiliation: Nutrition and Cancer Biology Laboratory, Jean-Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Liu
authors.affiliation: Nutrition and Cancer Biology Laboratory, Jean-Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Aizawa
authors.affiliation: Obesity and Metabolism Laboratory, Jean-Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Greenberg
authors.affiliation: Nutrition and Cancer Biology Laboratory, Jean-Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Ausman
authors.affiliation: Nutrition and Cancer Biology Laboratory, Jean-Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA. Electronic address: xiang-dong.wang@tufts.edu.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Wang
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002338:Carotenoids / Q000378:metabolism / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis* / Q000378:metabolism; D004032:Diet; D019587:Dietary Supplements; D004048:Diethylamines / Q000633:toxicity; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000009:adverse effects*; D005235:Fatty Liver, Alcoholic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D000077276:Lycopene; D018551:Solanum lycopersicum / Q000737:chemistry*; D051379:Mice; D047493:PPAR alpha / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011208:Powders; D051381:Rats
chemical_list: D004048:Diethylamines; D047493:PPAR alpha; D010936:Plant Extracts; D011208:Powders; D002338:Carotenoids; D000431:Ethanol; C031406:N-nitrodiethylamine; D019392:Cytochrome P-450 CYP2E1; D000077276:Lycopene
keywords: Alcohol; CYP2E1; Liver disease; Lycopene; Tomato