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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 | Power system parameter estimation: A survey显示文摘 | ZARCO P EXPOSITO A G | 2000 | IEEE Trans on Power Systems2000，15，1： | 1 |
| 3 | Changes in oxygenation indexes with the use of nitric oxide in the postoperative period of congenital heart disease surgery in patients with severe pulmonary hypertension显示文摘 | Ramirez L Calderon CJ Zarco ME | 2001 | Arch Cardiol Mex2001，71，： | 1 |
| 4 | Dis- criminating irrigated and rainfed olive orchards with thermal AS- TER imagery and DART 3 D simulation显示文摘 | Sepulere - Cant6a G Zarco - Tejada P J Sobrino J A | 2009 | Agricultural and Forest Meteorology2009，149，67： | 1 |
| 5 | Acute myeloblastic leukemia with minimal myeloid differentiation: phenotypical and ultrastructural characteristics显示文摘 | Villamor N Zarco MA Rozman M | 1998 | Leukemia1998，12，7： | 1 |
| 6 | Analysis of type T1 and T2 cytokines in patients with prostate cancer显示文摘 | Filella X Alcover J Zarco MA et at | 2000 | Prostate2000，44，4： | 1 |
| 7 | Acute myeloblastic leukemia with minimal myeloid differentiation:phenotypical and ultrastructural characteristics显示文摘 | Villamor N Zarco MA Rozma M | 1998 | Leukemia1998，12，： | 1 |
| 8 | Involve-ment of platelet activating factor and tumor necrosis fac-tor in the pathogenesis of joint inflammation in rabbits显示文摘 | Maestre C Herrero beaumont G | 1992 | Clin Exp Immunol1992，88，2： | 1 |
| 9 | Inci- dence of delayed ovulation in Holstein heifers and its effects on fertility and early luteal function显示文摘 | Herndndez-Cer6n J Zarco L Lima-Tamayo V | 1993 | Ther- iogenology1993，40，5： | 1 |
| 10 | Water Content of Estimention in Vegetation with MODIS Reflectance Data and Model Inversion Methods显示文摘 | Zarco T P J Rueda C A Ustin S L | 2003 | Remote Sensing of Enviroment2003，85，： | 1 |
| 11 | Analysis of type T1 and T2cytokines in patients with prostate cancer 显示文摘 | Alcover J Zarco MA | 2000 | Prostate2000，44，4： | 1 |
| 12 | Power system parameter estimation: A survey显示文摘 | Zarco P Exposito A G | 2000 | IEEE Trans on Power Systems2000，15，1： | 1 |
| 13 | Power system parameterestimation: a survey 显示文摘 | Zarco P Exposito A G | 2000 | IEEE Trans on Power Systems2000，15，1： | 1 |
| 14 | Lymphoepithelioma-like carcinoma of the skin显示文摘 | Ortiz-Frutos FJ Zarco C Gil R | 1993 | Clin Exp Dermatol1993，14，18： | 1 |
| 15 | Effect of fluorogestone acetate on embryo recovery and quality in eCG-superovulated goats with premature luteal regression显示文摘 | Espinosa-Marquez M C Valencia J Zarco L et ol | 2004 | Theriogenology2004，62，： | 1 |
| 16 | Deposition of Amorphous Carbon silver Composites显示文摘 | ZARCO O G RODIL S E CAMACHO-Lopez M A | 2009 | Thin Solid Films2009，，518： | 1 |
| 17 | GASI induces cell death through an intrinsic apoptotic pathway 显示文摘 | Zarco N Gonzalez-Ramirez R Gonzatlez R O | 2012 | Apoptosis2012，17，6： | 1 |
| 18 | Power System Parameter Estimation:A Survey显示文摘 | ZARCO P EXPOSITO A G | | 0，，01： | 1 |
| 19 | Changes in oxygenation indexes with the use of nitric oxide in the postoperative period of congenital heart disease surgery inpatients with severe pulmonary hypertension显示文摘 | Ramirez L Calderon Colmenero J Zarco Martinez E | 2001 | Arch Cardiol Mex2001，71，2： | 1 |
| 20 | Mapping canopy conductance and CWSI in olive orchards using high resolu- tion thermal remote sensing imagery 显示文摘 | Berni J A J Zarco - Tejada P J Scpulere - Cant6 G | 2009 | Remote Sensing of Envi- ronment2009，113，11： | 1 |
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