title: Protective Effects of Hydrolyzed Nucleoproteins from Salmon Milt against Ethanol-Induced Liver Injury in Rats.
abstract: Dietary nucleotides play a role in maintaining the immune responses of both animals and humans. Oral administration of nucleic acids from salmon milt have physiological functions in the cellular metabolism, proliferation, differentiation, and apoptosis of human small intestinal epithelial cells. In this study, we examined the effects of DNA-rich nucleic acids prepared from salmon milt (DNSM) on the development of liver fibrosis in an in vivo ethanol-carbon tetrachloride cirrhosis model. Plasma aspartate transaminase and alanine transaminase were significantly less active in the DNSM-treated group than in the ethanol plus carbon tetrachloride (CCl₄)-treated group. Collagen accumulation in the liver and hepatic necrosis were observed histologically in ethanol plus CCl₄-treated rats; however, DNSM-treatment fully protected rats against ethanol plus CCl₄-induced liver fibrosis and necrosis. Furthermore, we examined whether DNSM had a preventive effect against alcohol-induced liver injury by regulating the cytochrome p450 2E1 (CYP2E1)-mediated oxidative stress pathway in an in vivo model. In this model, CYP2E1 activity in ethanol plus CCl₄-treated rats increased significantly, but DNSM-treatment suppressed the enzyme's activity and reduced intracellular thiobarbituric acid reactive substances (TBARS) levels. Furthermore, the hepatocytes treated with 100 mM ethanol induced an increase in cell death and were not restored to the control levels when treated with DNSM, suggesting that digestive products of DNSM are effective for the prevention of alcohol-induced liver injury. Deoxyadenosine suppressed the ethanol-induced increase in cell death and increased the activity of alcohol dehydrogenase. These results suggest that DNSM treatment represents a novel tool for the prevention of alcohol-induced liver injury.
authors.affiliation: Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka 558-8585, Japan. kojima@life.osaka-cu.ac.jp.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kojima-Yuasa
authors.affiliation: Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka 558-8585, Japan. v-oooogue@ezweb.ne.jp.
authors.forename: Mayu
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka 558-8585, Japan. eri92011@gmail.com.
authors.forename: Eri
authors.initials: E
authors.lastname: Yoshikawa
authors.affiliation: Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka 558-8585, Japan. morimaru.y@gmail.com.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Morita
authors.affiliation: Life Science Institute Co., Ltd., Tokyo 103-0012, Japan. sekiguchi@life-science.co.jp.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sekiguchi
authors.affiliation: Life Science Institute Co., Ltd., Tokyo 103-0012, Japan. sutoh@life-science.co.jp.
authors.forename: Keita
authors.initials: K
authors.lastname: Sutoh
authors.affiliation: Life Science Institute Co., Ltd., Tokyo 103-0012, Japan. usumi@life-science.co.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Usumi
authors.affiliation: Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka 558-8585, Japan. yuasa-i@hotmail.co.jp.
authors.forename: Isao
authors.initials: I
authors.lastname: Matsui-Yuasa
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D003094:Collagen / Q000032:analysis; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000378:metabolism; D008107:Liver Diseases / Q000473:pathology; D008297:Male; D008954:Models, Biological; D009698:Nucleoproteins / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D012474:Salmon / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D009698:Nucleoproteins; D000431:Ethanol; D003094:Collagen; D004247:DNA; D002251:Carbon Tetrachloride; D019392:Cytochrome P-450 CYP2E1; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione
keywords: CYP2E1 activity; DNA-rich nucleic acid prepared from salmon milt (DNSM); alcohol-induced liver injury; collagen accumulation; in vivo ethanol-carbon tetrachloride cirrhosis model; plasma aminotransferases (AST and ALT); rats