Targeting dexamethasone to Kupffer cells: effects on liver inflammation and fibrosis in rats

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Barbro N MelgertKlaas Poelstra

Abstract

Kupffer cells (KC) play an important role in the pathogenesis of inflammatory liver diseases leading to fibrosis. Anti-inflammatory drugs are only effective when administered at high doses that may cause side effects. Therefore, dexamethasone coupled to mannosylated albumin (Dexa(5)-Man(10)-HSA) was designed by us to selectively deliver this anti-inflammatory drug to the KC. The effectiveness of Dexa(5)-Man(10)-HSA was studied both in organ cultures and fibrosis induced by bile duct ligation (BDL) in rats. Dexa(5)-Man(10)-HSA accumulated in livers of both healthy and fibrotic rats (67% +/- 5% and 70% +/- 9% of the dose, respectively) and uptake was found almost exclusively in KC. Active dexamethasone was liberated from its carrier, because Dexa(5)-Man(10)-HSA could effectively inhibit nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) release in endotoxin-activated liver slices. In vivo, however, this was associated with increased collagen I and III depositions and enhanced tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expression. This was accompanied by a decreased influx of reactive oxygen species (ROS) producing cells in the livers of BDL animals treated with Dexa(5)-Man(10)-HSA as compared with untreated ...Continue Reading

References

Jun 1, 1990·Kidney International·K PoelstraW W Bakker
Jun 16, 1986·Biochimica Et Biophysica Acta·J Hysing, H Tolleshaug
Aug 1, 1995·Seminars in Liver Disease·D K Meijer, G Molema
Apr 1, 1994·Journal of Bioenergetics and Biomembranes·J J Blum
Jan 1, 1994·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J A Spitzer
Dec 24, 1997·Journal of Pharmacological and Toxicological Methods·P OlingaG M Groothuis
Apr 2, 1998·Current Opinion in Immunology·P D Stahl, R A Ezekowitz
Apr 30, 1998·The Keio Journal of Medicine·K Decker
Aug 7, 1998·Digestion·G RamadoriB Saile
Aug 7, 1998·Digestion·M J Arthur
Aug 8, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·O ChazouillèresR Poupon
Apr 27, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·L BeljaarsK Poelstra
Jun 17, 1999·Alcoholism, Clinical and Experimental Research·H Tsukamoto
Jul 28, 1999·Seminars in Liver Disease·S L Friedman
Aug 10, 1999·Journal of Gastroenterology and Hepatology·D Li, S L Friedman
Nov 28, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·H YoshijiH Fukui
Nov 28, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·S L FriedmanD M Bissell
Jan 10, 1997·Toxicology in Vitro : an International Journal Published in Association with BIBRA·P OlingaG M Groothuis

❮ Previous
Next ❯

Citations

May 24, 2005·Digestive Diseases and Sciences·Costas XidakisElias Kouroumalis
Aug 12, 2009·Hepatology International·Angela DouglassMatthew C Wright
May 31, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jonas H GraversenSøren K Moestrup
Nov 29, 2013·BioMed Research International·Nidhi MishraSumit Arora
Mar 15, 2014·World Journal of Gastroenterology : WJG·Albert J Czaja
Jan 6, 2006·Anesthesiology·Alexander HoetzelBenedikt H J Pannen
Jun 26, 2015·Membranes·Jonas Heilskov Graversen, Søren Kragh Moestrup
Apr 30, 2014·Expert Opinion on Drug Delivery·Luigi FiumeGiuseppina Di Stefano
Jun 4, 2013·Nanomedicine : Nanotechnology, Biology, and Medicine·Michael FichterStephan Gehring
Jun 5, 2012·Acta Biomaterialia·Tracey M HintonKim Wark
Mar 1, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Klaas PoelstraLeonie Beljaars
May 25, 2010·Experimental Parasitology·Xu Wen-yueHuang Fu-sheng
Mar 27, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Felix HeymannFrank Tacke
Sep 21, 2007·Journal of Ethnopharmacology·Ching-Hsin HuangRong-Tsun Wu
Sep 16, 2005·Liver International : Official Journal of the International Association for the Study of the Liver·Rie SugimotoMakoto Nakamuta
Apr 30, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Flavia I CarrerasRaúl A Marinelli
Mar 16, 2005·Chemico-biological Interactions·Sung Hwan KiSang Geon Kim
Jan 15, 2014·Journal of Hepatology·Frank Tacke, Henning W Zimmermann
Nov 19, 2003·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Kazuhiko SuzukiKunio Doi
Nov 24, 2004·Biochemical and Biophysical Research Communications·Ursula BolkeniusLucia Wickert
Sep 26, 2012·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·I M WestraP Olinga
Feb 26, 2016·Cellular & Molecular Immunology·Cynthia Ju, Frank Tacke
Nov 12, 2002·The American Journal of Gastroenterology·Stephen A HarrisonSteven Schenker
Nov 2, 2011·Therapeutic Advances in Gastroenterology·Michal Cohen-Naftaly, Scott L Friedman
Sep 3, 2017·The Journal of Pharmacology and Experimental Therapeutics·Marlies SchippersKlaas Poelstra
Jan 10, 2020·Archives of Pharmacal Research·Shrawani Lamichhane, Sangkil Lee
Jun 30, 2016·Molecular Endocrinology·Kang Ho KimDavid D Moore
Dec 15, 2006·World Journal of Gastroenterology : WJG·George KoliosElias Kouroumalis
Apr 24, 2004·Clinical Science·Marieke H Schoemaker, Han Moshage

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here