File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Conference Paper: Cyclooxygenase-2 inhibitors attenuate the severity of galactosamine-lipopolysaccharide induced acute liver injury in mice

TitleCyclooxygenase-2 inhibitors attenuate the severity of galactosamine-lipopolysaccharide induced acute liver injury in mice
Authors
Issue Date2007
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep
Citation
The 42nd Annual Meeting of the European Association for the Study of the Liver, Barcelona, Spain, 11-15 April 2007. In Journal of Hepatology, 2007, v. 46 n. S1, p. S279 Abstract no. 741 How to Cite?
AbstractBackground and Aims: Cyclooxygenase (COX) is a key enzyme that converts arachidonic acid to PGH2, which is then converted to a series of end products such as PGE2 and thromboxanes. COX has two isoforms; COX- I (constitutively expressed) and COX-2 (inducible form). We investigated the role of COX inhibitors on the lethality, hepatic injury and inflammatory mediators induced by LPS in Galactosamine-sensitized mice. Methods: Adult male ICR mice were given a single i.p. injection of 600mg/kg of Galactosamine (Gal) and 20~g/kg of LPS. COX-2 inhibitors (indomethacin, 3 mg/kg or Nimesulide, 30 mgikg) were given 30 minutes before Gal/LPS injection. Corresponding negative (vehicle only) and positive control (Gal-LPS only) groups were also included. Sixteen hours after injection, the mice were killed. Liver tissue and blood were obtained. Histology (H&E staining), serum ALT, TBARS, RT-PCR, immunohistochemistry and Western Blotting for TNF-a, COX-1, COX-2, iNOS, nitrotyrosine and CIEBP-a and gel shift analysis for NF-KB were performed. Results: There was a marked reduction in the degree of hepatic necrosis in the indomethacin and (INDO) and Nimesulide-pretreated (NIM) mice when compared with the positive controls. Histological changes were confirmed by serum ALT levels. A significant reduction (p i 0.05) in hepatic oxidative and nitrosative stress [TBARS, iNOS mRNA and protein and nitrotyrosine protein] was observed in mice pre-treated with either INDO or NIM when compared with positive controls. There was an inverse relationship between COX-1 and COX-2 mRNAs and protein as well as between COX-2 and C/EBP-a protein expression in both the COX-2 inhibitor-pretreated mice and controls. TNF-a mRNA and NF-KB expression were also markedly higher in the positive controls when compared with the COX-2 inhibitor-pretreated mice. Conclusion: COX-2 inhibitors protected the liver from Gal-LPS induced hepatotoxicity as shown by a significant reduction in hepatic necrosis and serum ALT and oxidative stress. A marked reduction of iNOS, nitrotyrosine, TBARS, TNF-a and NF-KB expression was also observed, suggesting the use of COX inhibitors as therapeutic agents in preventing acute liver injury.
Persistent Identifierhttp://hdl.handle.net/10722/95355
ISSN
2015 Impact Factor: 10.59
2015 SCImago Journal Rankings: 4.570

 

DC FieldValueLanguage
dc.contributor.authorTipoe, GLen_HK
dc.contributor.authorLiong, ECen_HK
dc.contributor.authorLeung, TMen_HK
dc.contributor.authorLau, TYen_HK
dc.contributor.authorNanji, AAen_HK
dc.date.accessioned2010-09-25T15:59:34Z-
dc.date.available2010-09-25T15:59:34Z-
dc.date.issued2007en_HK
dc.identifier.citationThe 42nd Annual Meeting of the European Association for the Study of the Liver, Barcelona, Spain, 11-15 April 2007. In Journal of Hepatology, 2007, v. 46 n. S1, p. S279 Abstract no. 741en_HK
dc.identifier.issn0168-8278en_HK
dc.identifier.urihttp://hdl.handle.net/10722/95355-
dc.description.abstractBackground and Aims: Cyclooxygenase (COX) is a key enzyme that converts arachidonic acid to PGH2, which is then converted to a series of end products such as PGE2 and thromboxanes. COX has two isoforms; COX- I (constitutively expressed) and COX-2 (inducible form). We investigated the role of COX inhibitors on the lethality, hepatic injury and inflammatory mediators induced by LPS in Galactosamine-sensitized mice. Methods: Adult male ICR mice were given a single i.p. injection of 600mg/kg of Galactosamine (Gal) and 20~g/kg of LPS. COX-2 inhibitors (indomethacin, 3 mg/kg or Nimesulide, 30 mgikg) were given 30 minutes before Gal/LPS injection. Corresponding negative (vehicle only) and positive control (Gal-LPS only) groups were also included. Sixteen hours after injection, the mice were killed. Liver tissue and blood were obtained. Histology (H&E staining), serum ALT, TBARS, RT-PCR, immunohistochemistry and Western Blotting for TNF-a, COX-1, COX-2, iNOS, nitrotyrosine and CIEBP-a and gel shift analysis for NF-KB were performed. Results: There was a marked reduction in the degree of hepatic necrosis in the indomethacin and (INDO) and Nimesulide-pretreated (NIM) mice when compared with the positive controls. Histological changes were confirmed by serum ALT levels. A significant reduction (p i 0.05) in hepatic oxidative and nitrosative stress [TBARS, iNOS mRNA and protein and nitrotyrosine protein] was observed in mice pre-treated with either INDO or NIM when compared with positive controls. There was an inverse relationship between COX-1 and COX-2 mRNAs and protein as well as between COX-2 and C/EBP-a protein expression in both the COX-2 inhibitor-pretreated mice and controls. TNF-a mRNA and NF-KB expression were also markedly higher in the positive controls when compared with the COX-2 inhibitor-pretreated mice. Conclusion: COX-2 inhibitors protected the liver from Gal-LPS induced hepatotoxicity as shown by a significant reduction in hepatic necrosis and serum ALT and oxidative stress. A marked reduction of iNOS, nitrotyrosine, TBARS, TNF-a and NF-KB expression was also observed, suggesting the use of COX inhibitors as therapeutic agents in preventing acute liver injury.-
dc.languageengen_HK
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhepen_HK
dc.relation.ispartofJournal of Hepatologyen_HK
dc.rightsJournal of Hepatology. Copyright © Elsevier BV.en_HK
dc.titleCyclooxygenase-2 inhibitors attenuate the severity of galactosamine-lipopolysaccharide induced acute liver injury in miceen_HK
dc.typeConference_Paperen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0168-8278&volume=&spage=S279 #741&epage=&date=2006&atitle=Cyclooxygenase-2+inhibitors+attenuate+the+severity+of+galactosamine-lipopolysaccharide+induced+acute+liver+injury+in+miceen_HK
dc.identifier.emailTipoe, GL: tgeorge@hkucc.hku.hken_HK
dc.identifier.emailLiong, EC: eclionga@HKUCC.hku.hken_HK
dc.identifier.emailLeung, TM: leungtm@hkucc.hku.hken_HK
dc.identifier.emailLau, TY: andytylau@hotmail.comen_HK
dc.identifier.authorityTipoe, GL=rp00371en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/S0168-8278(07)62339-3-
dc.identifier.hkuros136080en_HK
dc.identifier.spage279en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats