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| 1 | Naringenin prevents experimental liver fibrosis by blocking TGFβ-Smad3 and JNK-Smad3 pathways显示文摘AIM To study the molecular mechanisms involved in the hepatoprotective effects of naringenin(NAR)on carbon tetrachloride(CCl4)-induced liver fibrosis.METHODS Thirty-two male Wistar rats(120-150 g)were randomly divided into four groups:(1)a control group(n=8)that received 0.7%carboxy methyl-cellulose(NAR vehicle)1 m L/daily p.o.;(2)a CCl4 group(n=8)that received 400 mg of CCl4/kg body weight i.p.3 times a week for 8 wk;(3)a CCl4+NAR(n=8)group that received 400 mg of CCl4/kg body weight i.p.3times a week for 8 wk and 100 mg of NAR/kg body weight daily for 8 wk p.o.;and(4)an NAR group(n=8)that received 100 mg of NAR/kg body weight daily for 8 wk p.o.After the experimental period,animals were sacrificed under ketamine and xylazine anesthesia.Liver damage markers such as alanine aminotransferase(ALT),alkaline phosphatase(AP),γ-glutamyl transpeptidase(γ-GTP),reduced glutathione(GSH),glycogen content,lipid peroxidation(LPO)and collagen content were measured.The enzymatic activity of glutathione peroxidase(GPx)was assessed.Liver histopathology was performed utilizing Masson’s trichrome and hematoxylin-eosin stains.Zymography assays for MMP-9 and MMP-2 were carried out.Hepatic TGF-β,α-SMA,CTGF,Col-I,MMP-13,NF-κB,IL-1,IL-10,Smad7,Smad3,p Smad3 and p JNK proteins were detected via western blot.RESULTS NAR administration prevented increases in ALT,AP,γ-GTP,and GPx enzymatic activity;depletion of GSH and glycogen;and increases in LPO and collagen produced by chronic CCl4 intoxication(P<0.05).Liver histopathology showed a decrease in collagen deposition when rats received NAR in addition to CCl4.Although zymography assays showed that CCl4 produced an increase in MMP-9 and MMP-2gelatinase activity;interestingly,NAR administration was associated with normal MMP-9 and MMP-2 activity(P<0.05).The anti-inflammatory,antinecrotic and antifibrotic effects of NAR may be attributed to its ability to prevent NF-κB activation and the subsequent production of IL-1 and IL-10(P<0.05).NAR completely prevented the increase in TGF-β,α-SMA,CTGF,Col-1,and MMP-13 proteins compared with the CCl4-treated group(P<0.05).NAR prevented Smad3phosphorylation in the linker region by JNK since this flavonoid blocked this kinase(P<0.05).CONCLUSION NAR prevents CCl4 induced liver inflammation,necrosis and fibrosis,due to its antioxidant capacity as a free radical inhibitor and by inhibiting the NF-κB,TGF-β-Smad3 and JNK-Smad3 pathways. | Erika Hernández-Aquino Natanael Zarco Sael Casas-Grajales Erika Ramos-Tovar Rosa E Flores-Beltrán Jonathan Arauz Mineko Shibayama Liliana Favari Víctor Tsutsumi José Segovia Pablo Muriel | 2017 | World Journal of Gastroenterology2017，23，24： | 10 |
| 2 | Probucol inhibits ABCA1-Mediated cellular lipid efflux显示文摘 | Favari E Zanotti I Zimetti F | 2004 | Arterioscler Thromb Vasc Biol2004，24，12： | 1 |
| 3 | Probucol inhibits ABCAl-mediated cellular lipid efflux 显示文摘 | Favari E Zanotti I Zimetti F | 2004 | Arterioscler Thromb Vase Biol2004，24，12： | 1 |
| 4 | Depletion of pre-beta-high density lipoprotein by human chymase impairs ATP-binding cassette transporter A1-but not scavenger receptor class B type I-mediated lipid efflux to high density lipoprotein显示文摘 | Favari E Lee M Calabresi L | 2004 | J Biol Chem2004，279，： | 1 |
| 5 | The Cteminal Domain of Apolipoprotein in AI is involved in ABCA1 driven Phospho lipid and Cholesterol efflux显示文摘 | Favari E Bernni F Tarugi P | | 0，，05： | 1 |
| 6 | Cellular cholesterol flux studies:methodological considerations显示文摘 | Rothblat GH de la Llera-Moya M Favari E | | 0，，01： | 1 |
| 7 | Inflammation impairs eNOS acti- vation by HDL in patients with acute coronary syndrome 显示文摘 | Gomaraschi M Ossoli A Favari E | 2013 | Cardiovascular Research2013，100，1： | 1 |
| 8 | Pitavastatin increases ABCA1-mediated lipid efflux from Fu5AH rat hepatoma cells显示文摘 | Zanotti I Favari E Sposito AC | 2004 | Biochem Biophys Res Commun2004，321，： | 1 |
| 9 | Depletion of pre-beta-high density lipoprtotein by human chymase impairs ATP-hinding cassette transporter Al-bat not scavenger receptor class B type I-mediated lipid efflux to high density lipoprotein 显示文摘 | Favari E Lee M Calabresi L | 2004 | J Biol Chem2004，279，： | 1 |
| 10 | Cholesterol efflux and reverse cholesterol transport 显示文摘 | Favari E Chroni A Tietge UJ | 2015 | Hcmdb Exp Pharmacol2015，224，： | 1 |
| 11 | Prevention of CCl4 induced liver cirrhosis by silymarin显示文摘 | Mourelle M Muriel P Favari L | 1989 | Fundam Clin Pharmacol1989，3，： | 1 |
| 12 | Molecular epidemiology ofmetieillin-resistant Staphylococcus aureus in Italian cysticfibrosis patients: a national overview显示文摘 | Cocchi P Cariani L Favari F | 2011 | J Cyst Fibros2011，10，6： | 1 |
| 13 | Prevention of CC14 induced liver cirrhosis by silymarin显示文摘 | Mourclle M Muriel P Favari L | 1989 | Fundam Clin Pharmaeol1989，3，： | 1 |
| 14 | Cellular cholesterol flux studies: methodological considerations 显示文摘 | Rothblat GH de la Llera-Moya M Favari E | 2002 | Atherosclerosis2002，163，1： | 1 |
| 15 | Comparison of the MB/BacT and BACTEC460 TB system for recovery of Mycobacteria from various clinical specimens显示文摘 | Brunello F Favari F Fontana R | 1999 | J Clin Microbiol1999，37，4： | 1 |
| 16 | Probucol inhibits ABCAl-mediated cellular lipid efflux 显示文摘 | Elda Favari Ilaria Zanotti Francesca Zimetti | 2004 | J Arterioscler Thromb Vasc Biol2004，24，： | 1 |
| 17 | Scavenger receptor class B type I affects cholesterol homeostasis by magnifying cholesterol flux between cells and HDL显示文摘 | de La Llera-Moya M Connelly MA Drazul D Klein SM Favari E Yancey PG | 2001 | J Lipid Res2001，42，12： | 1 |
| 18 | Erythrocytealterations correlate with CCl4 and biliary obstruction-induced liver damage in the rat显示文摘 | Muriel P Favari L Soto C | 1993 | Life Sci1993，52，： | 1 |
| 19 | Inflammation impairs eNOS activation by HDL in patients with acute coronary syndrome显示文摘 | Monica Gomaraschi Alice Ossoli Elda Favari Maria Pia Adorni Gianfranco Sinagra Luigi Cattin Fabrizio Veglia Franco Bernini Guido Franceschini Laura Calabresi | 2013 | Cardiovascular Research2013，，1： | 1 |
| 20 | Impact of system in- flammation and autoimmue disease on apoA- 1 and HDL plasma levels and functions 显示文摘 | Monteucco F Favari E Norata GD | 2015 | Handb Exp Pharmacol2015，224，： | 1 |
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