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| 1 | pregnane X receptor and constitutive androstane receptor modulate differently CYp3A-mediated metabolism in earlyand late-stage cholestasis显示文摘AIM To ascertain whether cholestasis affects the expression of two CYP3 A isoforms(CYP3 A1 and CYP3 A2) and of pregnane X receptor(PXR) and constitutive androstane receptor(CAR).METHODS Cholestasis was induced by bile duct ligation in 16 male Wistar rats; whereas 8 sham-operated rats were used as controls. Severity of cholestasis was assessed on histological examination of liver sections, and serum concentrations of albumin, AST, ALT, GGT, ALPK and bilirubin. Gene and protein expressions of PXR, CAR, CYP3 A1 and CYP3 A2 were assessed by means of q RT-PCR and Western blot, respectively. Alterations in CYP3 A activity were measured by calculating the kinetic parameters of 4-OH and 1'-OH-midazolam hydroxylation, marker reactions for CYP3 A enzymes.RESULTS The m RNA and protein expression of CYP3 A1 increased significantly in mild cholestasis(P < 0.01). At variance, m RNA and protein expression of CYP3 A2 didn't change in mild cholestasis, whereas the expression and activity of both CYP3 A1 and CYP3 A2 decreased dramatically when cholestasis became severe. Consistently with these observations, the nuclear expression of both PXR and CAR, which was measured because they both translocate into the cell nucleus after their activation, virtually disappeared in the late stage of cholestatic injury, after an initial increase. These results indicate that early-and late-stage cholestasis affects CYP3 Amediated drug metabolism differently, probably as consequence of the different activation of PXR and CAR.CONCLUSION Early-and late-stage cholestasis affects CYP3 Amediated drug metabolism differently. PXR and CAR might be targeted therapeutically to promote CYP3 Amediated liver detoxification. | Daniela Gabbia Arianna Dalla Pozza Laura Albertoni Roberta Lazzari Giorgia Zigiotto Maria Carrara Vincenzo Baldo Tatjana Baldovin Annarosa Floreani Sara De Martin | 2017 | World Journal of Gastroenterology2017，23，42： | 5 |
| 2 | Y chromosome loss in male patients with primary biliary cirrhosis显示文摘 | Ana Lleo Sabine Oertelt-Prigione Ilaria Bianchi Lisa Caliari Palma Finelli Monica Miozzo Roberta Lazzari Annarosa Floreani Francesca Donato Massimo Colombo M. Eric Gershwin Mauro Podda Pietro Invernizzi | 2013 | Journal of Autoimmunity2013，，： | 2 |
| 3 | A PC model for selecting mud cropping farm machinery systems 显示文摘 | Massimo Lazzari Fabrizio Mazzetto | 1996 | Computers and Electronics in Agriculture1996，14，1： | 1 |
| 4 | Comparison of different serumfree media for ex vivo expansion of HPCs from cord blood using thrombopoietin, Flt-3 ligand, IL-6, and IL-11 显示文摘 | Lazzari L Lucchi S Porretti L | 2001 | Transfusion2001，41，： | 1 |
| 5 | Cord blood plasma mediated ex vivo expansion of hematopoictic progenitor ceus显示文摘 | Bertolini F Lazzari L Lann E | 1994 | BMT1994，14，： | 1 |
| 6 | One-pot preparation of gold-elastomer nanocompositas using PDMS- grafl-PEO copolymcr micelles as nanoreactors显示文摘 | Hoppe C E Rodriguez-Abreu C Lazzari M | 2008 | Physica Status Solidi Applied Research2008，205，6： | 1 |
| 7 | Histopathological a- nalysis of the olfactory epithelium of zebrafish ( Danio rerio) exposed to sublethal doses of urea显示文摘 | Bettini S Lazzari M Ferrando S | 2016 | J Anat2016，228，1： | 1 |
| 8 | Glial fibrillary acidic protein and vimentin immunoreactivity of astroglial cells in the central nervous system of adult Podarcis sicula (Squamata, Lacertidae) 显示文摘 | Franceschini V | 2001 | J Anat2001，198，1： | 1 |
| 9 | Digital field -oriented control for dual three-phase induction motor drives 显示文摘 | BOJOI R LAZZARI M PROFUMO F | 2003 | IEEE Transactions on Industry Applications2003，，3： | 1 |
| 10 | Evaluation of the effect of cryopreservation on exvivo expasion of hematopoietic progenitors from cord blood显示文摘 | Lazzari L Lucchi S Montemurro T | 2001 | Bone Marrow Transplant2001，28，7： | 1 |
| 11 | Digital field-oriented control for dual three-phase induction motor drives显示文摘 | Bojoi R Lazzari M Profumo F | 2003 | IEEE Transactions on Industry Applications2003，，3： | 1 |
| 12 | Non- linear dynamic analysis of cable-suspended structures subjected to wind actions 显示文摘 | LAZZARI M SAETTA A V VITALIANI R V | 2001 | Computers and Structures2001，79，9： | 1 |
| 13 | Transbronchial needle aspiration improve the diagnostic yield of bronchoscopy in sarcoidosis 显示文摘 | Trisolini R Lazzari agli L Cancellieri A | 2004 | Sarcoidosis Vasc Diffuse Lung Dis2004，21，2： | 1 |
| 14 | Predicting iron losses in soft magnetic materials with arbitrary voltage supply:an engineering approach显示文摘 | Aldo Boglietti Andrea Cavagnino Mario Lazzari | 2007 | IEEE Transactions on Magnetics2007，39，2： | 1 |
| 15 | A new GIS-based integratedapproach to analyse the anthropic-geomorphological risk andrecover the vernacular architecture显示文摘 | Lazzari M Danese M Masini N | 2009 | Journal of CulturalHeritage2009，，： | 1 |
| 16 | Birth of cloned pigs from zona free nuclear transfer blastocysts developed in vitro before transfer 显示文摘 | Lagutina I Lazzari G Galli C | 2006 | Cloning and Stem Cells2006，8，4： | 1 |
| 17 | Polymer compatibilization effects in the thermal degradation of blends containing SAN and EPDM polymers显示文摘 | Chiantore O Trossarelli L Lazzari M | 1998 | Polymer1998，39，13： | 1 |
| 18 | Wind field simulation for structural engineering purposes显示文摘 | Rossi R Lazzari M Vitaliani R | 2004 | International Journal for Numerical Methods in Engineering2004，61，5： | 1 |
| 19 | Long-term expansion and maintenance of cord blood haematopoietic stem cells using thrombopoietin,Flt3-ligand, interleukin-6 and IL-11 in a serum-free and stroma-free culture system显示文摘 | Lazzari L Lucchi S Rebulla P | 2001 | Hematology2001，112，： | 1 |
| 20 | Digital field-oriented control for dual three-phase induction motor drives显示文摘 | Bojoi R Lazzari M Profumo F | 2003 | IEEE Transactions on Industry Applications2003，39，3： | 1 |
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