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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 | Arsenic and fluoride in the groundwater of Mexico显示文摘 | Armienta M A Segovia N | 2008 | Environmental Geochemistry and Health2008，30，： | 1 |
| 3 | Oc- currence of priority pollutants in WWTP effluents and Mediterra- nean coastal waters of Spain 显示文摘 | Martf N Aguado D Segovia - Martinez L | 2011 | Marine Pollution Bulletin2011，62，3： | 1 |
| 4 | Authentication of commercial- ized crab-meat in Chile using DNA barcoding 显示文摘 | Haye P A Segovia N I Vera R | 2012 | Food Control2012，25，1： | 1 |
| 5 | Rejection after conversion to a proliferation signal inhibitor in chronic heart transplantation显示文摘 | Francisco González‐Vílchez José A. Vázquez de Prada María J. Paniagua Luis Almenar Sonia Mirabet Manuel Gómez‐Bueno Beatriz Díaz‐Molina Jose M. Arizón Juan Delgado Félix Pérez‐Villa María G. Crespo‐Leiro Luis Martínez‐Dolz Eulalia Roig Javier Segovia José | 2013 | Clin Transplant2013，，6： | 1 |
| 6 | A technical, economical and market review of organic Rankine cycles for the conversion of low-grade heat for power generation显示文摘 | Fredy Vélez José J. Segovia M. Carmen Martín Gregorio Antolín Farid Chejne Ana Quijano | 2012 | Renewable and Sustainable Energy Reviews2012，，6： | 1 |
| 7 | HLA in Chileana with intrahepatic cholestasis of pregnancy显示文摘 | Reyes H Wegmann ME Segovia N | 1982 | Hepatology1982，2，4： | 1 |
| 8 | Authentication of commercialized crab-meat in Chile using DNA barcoding 显示文摘 | Haye P A Segovia N I Vera R | 2012 | Food Control2012，25，1： | 1 |
| 9 | High-pressure isobaric heat capacities using a new flow calorimeter显示文摘 | José J. Segovia David Vega-Maza César R. Chamorro M. Carmen Martín | 2008 | The Journal of Supercritical Fluids2008，，3： | 1 |
| 10 | l-Theanine prevents carbon tetrachloride-induced liver fibrosis via inhibition of nuclear factor [kappa]B and down-regulation of transforming growth factor [beta] and connective tissue growth factor显示文摘 | JE Pérez-Vargas N Zarco P Vergara M Shibayama J Segovia V Tsutsumi P Muriel | 2016 | Human and Experimental Toxicology2016，，2： | 1 |
| 11 | Arsenic and fluoride in thegroundwater of Mexico 显示文摘 | ARMIENTA M A SEGOVIA N | 2008 | Environmental Geochemistry andHealth2008，30，4： | 1 |
| 12 | Heavy Metal Concentration in Surface Soils from Mexico City显示文摘 | O Morton-Bermea E Hemandez Aivarez I Gaso N Segovia | 2002 | Bull Environ Contam Toxicol2002，68，： | 1 |
| 13 | Authentication of commercialized crab-meat in Chile using DNA barcoding 显示文摘 | Haye P A Segovia N I Vera R | 2011 | Food Control2011，25，1： | 1 |
| 14 | Aging, plasticity and environmental en- richment :structural changes and neurotransmitter dynamics in several ar- eas of the brain显示文摘 | thruugtl environmental en- n the iTIotlse dentate gyrus Morn F Segovia G del Areo A | 2007 | Brain Res Rev2007，55，1： | 1 |
| 15 | Risk of Trypanosoma cruzi I (Kinetoplastida: Trypanosomatidae) transmission by Panstrongylus geniculatus (Hemiptera: Reduviidae) in Caracas (Metropolitan District) and neighboring States, Venezuela显示文摘 | Hernán J. Carrasco Annhymariet Torrellas Carlos García Maikell Segovia M.Dora Feliciangeli | 2005 | International Journal for Parasitology2005，，13： | 1 |
| 16 | Sequence analysis and phylogenetie relationship of genes encoding heterodimeric phospholipases A2 from the venom of the scorpion Anuroctonus phaiodactylus显示文摘 | Valdez-Cruz N A Segovia L Corona M | 2007 | Gene2007，396，： | 1 |
| 17 | Heavy metal concentration in surface Soil from mexico city 显示文摘 | MORTON - BERMEA E HEMANDEZ AIVAREZ I SEGOVIA G N | 2002 | Bull Environ Contam Toxicol2002，68，： | 1 |
| 18 | Learned immobility explains the behavior of rats in the forced swimming test显示文摘 | De Pablo JM Parra A Segovia S Guillamón A | | 0，，02： | 1 |
| 19 | Characteristics of patients with survival longer than 20 years following heart transplantation显示文摘 | Jaramillo N Segovia J Gomez-Bueno M | 2013 | Rev Esp Cardiol (Engl Ed)2013，66，10： | 1 |
| 20 | Measurement of the (pressure, density, temperature) relation of two (methane plus nitrogen) gas mixtures at temperatures between 240 and 400 K and pressures up to 20 MPa using an accurate single-sinker densimeter显示文摘 | Chamorro C R Segovia J J Martín M C Villama(~n)án M A Estela-Uribe J F Trusler J P M | | 0，，7： | 1 |
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