A silybin-phospholipids complex counteracts rat fatty liver degeneration and mitochondrial oxidative changes  

作　　者：Ignazio Grattagliano Catia V Diogo Maria Mastrodonato Ornella de Bari Michele Persichella David QH Wang Adriana Liquori Domenico Ferri Maria Rosaria Carratù Paulo J Oliveira Piero Portincasa 

机构地区：[1]Section of Internal Medicine,Department of Interdisciplinary Medicine,University of Bari,70124 Bari,Italy [2]Center for Neuroscience and Cell Biology,Largo Marques de Pombal,University of Coimbra,P-3004-517 Coimbra,Portugal [3]Laboratory of Histology and Comparative Anatomy,Department of Animal and Environmental Biology,University of Bari,70125 Bari,Italy [4]Division of Gastroenterology and Hepatology,Department of Internal Medicine,Edward Doisy Research Center,Saint Louis University School of Medicine,Saint Louis,MO 63104,United States [5]Department of Pharmacology and Human Physiology,University of Bari,70124 Bari,Italy

出　　处：《World Journal of Gastroenterology》2013年第20期3007-3017,共11页世界胃肠病学杂志（英文版）

基　　金：Supported by Grants from MIUR(Ministero Università e Ricerca Scientifica COFIN2006);"Fondi Ateneo Ricerca Scientifica 2005/2006" from the University of Bari,Italy

摘　　要：AIM:To investigate the effectiveness of antioxidant compounds in modulating mitochondrial oxidative alterations and lipids accumulation in fatty hepatocytes.METHODS:Silybin-phospholipid complex containing vitamin E(Realsil) was daily administered by gavage(one pouch diluted in 3 mL of water and containing 15 mg vitamin E and 47 mg silybin complexed with phospholipids) to rats fed a choline-deprived(CD) or a high fat diet [20% fat,containing 71% total calories as fat,11% as carbohydrate,and 18% as protein,high fat diet(HFD)] for 30 d and 60 d,respectively.The control group was fed a normal semi-purified diet containing adequate levels of choline(35% total calories as fat,47% as carbohydrate,and 18% as protein).Circulating and hepatic redox active and nitrogen regulating molecules(thioredoxin,glutathione,glutathione peroxidase),NO metabolites(nitrosothiols,nitrotyrosine),lipid peroxides [malondialdehyde-thiobarbituric(MDA-TBA)],and pro-inflammatory keratins(K-18) were measured on days 0,7,14,30,and 60.Mitochondrial respiratory chain proteins and the extent of hepatic fatty infiltration were evaluated.RESULTS:Both diet regimens produced liver steatosis(50% and 25% of liver slices with CD and HFD,respectively) with no signs of necro-inflammation:fat infiltration ranged from large droplets at day 14 to disseminated and confluent vacuoles resulting in microvesicular steatosis at day 30(CD) and day 60(HFD).In plasma,thioredoxin and nitrosothiols were not significantly changed,while MDA-TBA,nitrotyrosine(from 6 ± 1 nmol/L to 14 ± 3 nmol/L day 30 CD,P < 0.001,and 12 ± 2 nmol/L day 60 HFD,P < 0.001),and K-18(from 198 ± 20 to 289 ± 21 U/L day 30 CD,P < 0.001,and 242 ± 23 U/L day 60 HFD,P < 0.001) levels increased significantly with ongoing steatosis.In the liver,glutathione was decreased(from 34.0 ± 1.3 to 25.3 ± 1.2 nmol/mg prot day 30 CD,P < 0.001,and 22.4 ± 2.4 nmol/mg prot day 60 HFD,P < 0.001),while thioredoxin and glutathione peroxidase were initially increased and then decreased.Nitrosothiols were constanAIM: To investigate the effectiveness of antioxidant compounds in modulating mitochondrial oxidative alterations and lipids accumulation in fatty hepatocytes. METHODS: Silybin-phospholipid complex containing vitamin E (Realsil?) was daily administered by gavage (one pouch diluted in 3 mL of water and containing 15 mg vitamin E and 47 mg silybin complexed with phospholipids) to rats fed a choline-deprived (CD) or a high fat diet [20% fat, containing 71% total calories as fat, 11% as carbohydrate, and 18% as protein, high fat diet (HFD)] for 30 d and 60 d, respectively. The control group was fed a normal semi-purified diet containing adequate levels of choline (35% total calories as fat, 47% as carbohydrate, and 18% as protein). Circulating and hepatic redox active and nitrogen regulating molecules (thioredoxin, glutathione, glutathione peroxidase), NO metabolites (nitrosothiols, nitrotyrosine), lipid peroxides [malondialdehyde-thiobarbituric (MDA-TBA)], and pro-inflammatory keratins (K-18) were measured on days 0, 7, 14, 30, and 60. Mitochondrial respiratory chain proteins and the extent of hepatic fatty infiltration were evaluated. RESULTS: Both diet regimens produced liver steatosis (50% and 25% of liver slices with CD and HFD, respectively) with no signs of necro-inflammation: fat infiltration ranged from large droplets at day 14 to disseminated and confluent vacuoles resulting in microvesicular steatosis at day 30 (CD) and day 60 (HFD). In plasma, thioredoxin and nitrosothiols were not significantly changed, while MDA-TBA, nitrotyrosine (from 6 ± 1 nmol/L to 14 ± 3 nmol/L day 30 CD, P < 0.001, and 12 ± 2 nmol/L day 60 HFD, P < 0.001), and K-18 (from 198 ± 20 to 289 ± 21 U/L day 30 CD, P < 0.001, and 242 ± 23 U/L day 60 HFD, P < 0.001) levels increased significantly with ongoing steatosis. In the liver, glutathione was decreased (from 34.0 ± 1.3 to 25.3 ± 1.2 nmol/mg prot day 30 CD, P < 0.001, and 22.4 ± 2.4 nmol/mg prot day 60 HFD, P < 0.001), while thioredoxin and glutathione peroxidase were initia

关 键 词：Fatty liver Glutathione Lipid PEROXIDATION NITROSOTHIOLS NITROTYROSINE THIOREDOXIN 

分 类 号：R575.5[医药卫生—消化系统]