Dietary lycopene attenuates cigarette smoke-promoted nonalcoholic steatohepatitis by preventing suppression of antioxidant enzymes in ferrets |
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| Affiliation: | 1. Nutrition and Cancer Biology Lab, Jean Mayer USDA-Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, MA, USA;2. Nutritional Immunology Lab, JM USDA-HNRCA at Tufts University, Boston, MA, USA;3. Biochemical and Molecular Nutrition Program, Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA;4. Molecular Pathology Unit, Massachusetts General Hospital, Boston, MA, USA;1. Internal Medicine Department, Botucatu Medical School, Univ Estadual Paulista (UNESP), Botucatu, Brazil;2. Department of Surgery and Orthopedics, Botucatu Medical School, Univ Estadual Paulista (UNESP), Botucatu, Brazil;3. Department of Anesthesiology, Botucatu Medical School, Univ Estadual Paulista (UNESP), Botucatu, Brazil;4. Chemistry and Biochemistry Department, Institute of Biosciences, Univ Estadual Paulista (UNESP), Botucatu, Brazil;1. Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan;2. Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan,;3. Department of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, Taipei, Taiwan,;4. Research Center for Development Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan;1. Division of Nutritional Sciences, University of Illinois at Urbana-ChampaignUrbana, IL United States;2. Food Science and Human Nutrition, University of Illinois at Urbana-Champaign Urbana, IL United States;3. School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign Urbana, IL United States;4. Dorothy M. Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA;5. Illinois Informatics Institute, University of Illinois at Urbana-Champaign, Urbana, IL United States;1. Department of Biological Sciences, Laboratory of Experimental Pathophysiology, Federal University of Ouro Preto, Minas Gerais, Brazil;2. Department of Biological Sciences, Laboratory of Immunobiology of Inflammation, Federal University of Ouro Preto, Minas Gerais, Brazil;3. Department of Biological Sciences, Laboratory of Biochemistry and Molecular Biology, Federal University of Ouro Preto, Minas Gerais, Brazil;4. Department of Biological Sciences, Laboratory of Biomaterials and Experimental Pathology, Federal University of Ouro Preto, Minas Gerais, Brazil;5. Department of Biological Sciences, Laboratory of Metabolic Biochemistry, Federal University of Ouro Preto, Minas Gerais, Brazil;1. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel;2. Bert Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer, Israel;3. The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel-Hashomer, Israel;4. Achva Academic College, Israel;5. School of Psychology, Interdisciplinary Center (IDC) Herzliya, Herzliya, Israel;6. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, NY, USA;7. The Nehemia Rubin Excellence in Biomedical Research – The TELEM Program, Sheba Medical Center, Tel-Hashomer, Israel;1. United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota;2. School of Public Health and Health Sciences, University of Massachusetts, Amherst, Massachusetts;3. School of Food and Agriculture, University of Maine, Orono, Maine |
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| Abstract: | 
Cigarette smoke (CS) is an independent risk factor in development of nonalcoholic steatohepatitis (NASH) and fibrosis. Lycopene, a carotenoid naturally occurring in tomatoes, has been shown to be a protective agent against tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced NASH. In the present study using a ferret model we investigated whether CS promotes NASH and whether dietary lycopene can inhibit CS-promoted NASH development, and if so, what potential mechanisms were involved. Ferrets were divided into 4 groups (n=12−16/group): control, NNK/CS exposed, NNK/CS plus low-dose lycopene (2.2 mg/kg BW/day), and NNK/CS plus high-dose lycopene (6.6 mg/kg BW/day) groups, for 26 weeks. Results showed that hepatic steatosis, infiltrates of inflammatory cells, and the number and size of inflammatory foci in liver, together with key genes involved in hepatic fibrogenesis were higher in the NNK/CS group compared to the control group; a lycopene diet reversed these changes to the levels of the control group. Interestingly, a major lycopene cleavage enzyme, beta-carotene 9’,10’-oxygenase (BCO2), which recently has been recognized to play metabolic roles beyond cleavage function, was down-regulated by NNK/CS exposure, but this decrease was prevented by lycopene feeding. NNK/CS exposure also downregulated liver expression of antioxidant enzymes and upregulated oxidative stress marker, which were all prevented by lycopene. In conclusion, our results suggest that CS can promote development of NASH and liver fibrosis in ferrets, which is associated with downregulation of BCO2 and impairment of antioxidant system in liver; dietary lycopene may inhibit CS-promoted NASH by preventing suppression of BCO2 and decline in antioxidant network. |
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