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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 | Pathological factors related to lymph node metastasis of submucosally invasive gastric cancer: criteria for additional gastrectomy after endoscopic resection显示文摘 | Mototsugu Fujii Yutaro Egashira Hiroshi Akutagawa Tsukasa Nishida Toshikatsu Nitta Go Edagawa Yoshitaka Kurisu Yuro Shibayama | 2013 | Gastric Cancer2013，，4： | 3 |
| 3 | Vitamin K2 selectively induced apoptosis in ovarian TYK-nμ and pancreatic MIA PaCa-2 cells out of eight solid tumor cell lines through a mechanism different from geranylgeraniol显示文摘 | Shibayama Imaau T Sakairi S Watanabe A | | J Cancer Res Clin Oncol0，，： | 2 |
| 4 | Experimental Amebiasis: A Selected Review of Some In Vivo Models显示文摘 | Víctor Tsutsumi Mineko Shibayama | 2006 | Archives of Medical Research2006，，2： | 2 |
| 5 | A novel process for recovery of tungsten and vanadium from a leach solution of tungsten alloy scrap显示文摘 | Luo T L Miyazaki Shibayama A | 2003 | Minerals Engineering2003，16，： | 1 |
| 6 | Studies on pH and temperature dependence of the dynamics and heterogenities in poly (N-isopropylacrylamide-co-so- dium acrylate) gels显示文摘 | Tatsuya Motonaga Mitsuhiro Shibayama | 2002 | Polymer2002，43，： | 1 |
| 7 | Removal of Antimony Ion from Artificial Wastewater with Lead Compounds显示文摘 | Uchida A Koyanaka K Shibayama A | 2003 | Shigen-to-Sozai2003，119，： | 1 |
| 8 | Slide-ring gel:Topological gel with freely movable cross-links显示文摘 | Takeshi Karino Mitsuhiro Shibayama Kohzo Ito | 2006 | Physica B:Condensed Matter In Press Corrected Proof2006，26，： | 1 |
| 9 | Immunophenotypic features and configuration of immunoglobulin genes in hairy cell leukemia-Japanese variant显示文摘 | Yamaguchi M Machii T Shibayama H | 1996 | Leukemia1996，10，： | 1 |
| 10 | Identification of a cytokine-induced antiapoptotic molecule anamorsin essential for definitive hematopoiesis显示文摘 | Shibayama H Takai E Matsumura I | 2004 | J Exp Med2004，199，： | 1 |
| 11 | Preparation and properties of keratin-poly(vinyl alcohol) blend fiber 显示文摘 | KATOH K SHIBAYAMA M TANABE T | 2004 | Journal of Applied Polymer Science2004，91，2： | 1 |
| 12 | Vertical distribution of suspended sediment concentration in and outside surf zone显示文摘 | Tomoya Shibayama Rattanapikon Winyu | 1993 | Coastal Engineering1993，36，1： | 1 |
| 13 | Academic entrepre- neurship and exchange of scientific resources: Materi- al transfer in life and materials sciences in Japanese universities显示文摘 | Shibayama S Walsh J P Baba Y | 2012 | American Sociological Review2012，，7： | 1 |
| 14 | Combination of nedaplatin and vindesine for the treatment of relapsed or refractory non-small cell lung cancer (NSCLC)显示文摘 | K Fujiwara N Takigawa Y Segawa K Eguchi T Shibayama K Kiura H Ueoka M Harada | 2000 | Lung Cancer2000，，1： | 1 |
| 15 | Extremely Low Tem-perature Coefficient of Resistance in Anti-perovskite Mn^ Ag| _xCu,N显示文摘 | Takenaka K Ozawa A Shibayama T | 2011 | Applied Physics Letters2011，98，02： | 1 |
| 16 | A nearshore wave breaking-model显示文摘 | Li S Wang S Shibayama T | 1998 | Acta Oceanological Sinica1998，17，1： | 1 |
| 17 | Estimating grain yield of maturing rice canopies using high spectral resolution reflectance measurements 显示文摘 | Michio Shibayama Tsuyoshi Akiyama | 1991 | Remote Sensing of Environment1991，36，： | 1 |
| 18 | Effect of mierostructure on oxidation resistance of MoSi2 fabricated by spark plasma sintering显示文摘 | Jyunichi Kuehino Kazuya Kurokawa Tamaki Shibayama | 2004 | Vacuum2004，73，： | 1 |
| 19 | 显示文摘 | Miyamoto T Shibayama K | 1973 | Journal of Applied Physics1973，44，： | 1 |
| 20 | Immature platelet fraction for prediction of platelet engraftment after allogeneic stem cell transplantation显示文摘 | Takami A Shibayama M Orito M | 2007 | Bone Marrow Transplant2007，39，8： | 1 |
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