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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 | Vibrant soundbridge in congenital osseous atresia: multicenter study of' 12 patients with osseous atrcsia 显示文摘 | Zemotti M E Arauz S L Di Gregorio M F | 2013 | Acta Otolaryngol2013，133，6： | 1 |
| 3 | Effects of hook offsets on target species catch rates and sea turtle bycatch in a shallow Costa Rican longline fishery 显示文摘 | Swimmer Y Wang J Arauz R | 2010 | Aquatic Conservation: Marine Freshwater Ecosystem2010，10，4： | 1 |
| 4 | Genotype H: a new Amerindian genotype of hepatitis B virus revealed in Central America显示文摘 | Norder H Robertson BH Magnius LO | 2002 | J Gen Virol2002，83，8： | 1 |
| 5 | Analysis of two- phase flow in cryogenic damper seals-Part I: Theoretical model显示文摘 | Arauz Grigory L San Andres Luis | 1997 | American Society of Mechanical Engineers (Paper)1997，，： | 1 |
| 6 | Cerebrovascular complica- tions during pregnancy and postpartum ? clinical and prognosis obser- vations in 240 Hispanic women显示文摘 | Cantu-Brito C Arauz A Aburto Y | 2011 | Eur J Neurol2011，18，6： | 1 |
| 7 | Genotype H : a new Amerindian genotype of hepatitis B virus revealed in Central America显示文摘 | Arauz Ruiz P Norder H Robertson BH | 2002 | J Gen Virol2002，83，8： | 1 |
| 8 | Vibrant Soundbridge in congenital osseous atresia: multicenter study of 12 patients with osseous atresia显示文摘 | Mario E. Zernotti Santiago L. Arauz Maria Fernanda Di Gregorio Santiago A. Arauz Paola Tabernero M. Celeste Romero | 2013 | Acta Oto-Laryngologica2013，，6： | 1 |
| 9 | Prospective study of single and multiple lacunar infarcts using magnetic resonance imaging 显示文摘 | Arauz A Murillo L Cantu L | 2003 | Stroke2003，34，： | 1 |
| 10 | Nisin Biotechnological Production and Application显示文摘 | De Arauz L J Jozala A F Mazzola P G | 2009 | Trends Food Science and Technology2009，20，34： | 1 |
| 11 | Prospective study of single and multiple lacunar infarcts using magnetic resonance imaging: risk factors, recurrence, and outcome in 175 consecutive cases 显示文摘 | Arauz A Murfllo L Can C | 2003 | Stroke2003，34，： | 1 |
| 12 | Predictive factors for intracerebral hemorrhage in patients with cavernous angiomas显示文摘 | Cantu C Murillo-Bonilla L Arauz A | 2005 | Neurol Res2005，27，3： | 1 |
| 13 | Dissection of cervical arteries:Long-term follow-up study of 130 conscutive cases 显示文摘 | Arauz A Hoyos L Espinoza C | 2006 | Cerebrovasc Dis2006，22，23： | 1 |
| 14 | Cerebral venous thrombosis: a diagnostic and treatment update 显示文摘 | Guenther G Arauz A | 2011 | Neurologia2011，26，8： | 1 |
| 15 | Dissectiion of cervical arteries: long-term follow-up study of 130 consecutive cases显示文摘 | Arauz A Hoyos L Espinoza C | 2006 | Cerebrovasc Dis2006，22，： | 1 |
| 16 | Analysis of two-phase flow in cryogenic damper seals - Part Ⅰ: Theoretical model显示文摘 | Arauz Grigory L San Andres Luis | 1997 | American Society of Mechanical Engineers (Paper)1997，，： | 1 |
| 17 | Mild hyperhomocysteinemia and low folate concentrations as risk factors for cervical arterial dissection显示文摘 | ARAUZ A HOYOS L CANTI C | 2007 | Cerebrovasc Dis2007，24，23： | 1 |
| 18 | Prospective study of single and multiple lacunar infarcts using magnetic resonance imaging:risk factors,recurrence,and outcome in 175 consecutive cases显示文摘 | Arauz A Murillo L Cantu C | 2003 | Storke2003，，： | 1 |
| 19 | Cerebral venous thrombosis:a diagnostic and treatment update显示文摘 | GUENTHER G ARAUZ A | | 0，，08： | 1 |
| 20 | The medical home: relationships with family fun- ctioning for children with and without special health care needs 显示文摘 | Arauz B A D Van C J M Gnanasekaran S K | 2012 | Academic Pediatrics2012，12，5： | 1 |
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