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Article: FK 409 ameliorates small-for-size liver graft injury by attenuation of portal hypertension and down-regulation of Egr-1 pathway

TitleFK 409 ameliorates small-for-size liver graft injury by attenuation of portal hypertension and down-regulation of Egr-1 pathway
Authors
Issue Date2004
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.annalsofsurgery.com
Citation
Annals Of Surgery, 2004, v. 240 n. 1, p. 159-168 How to Cite?
AbstractObjective: To investigate whether low-dose nitric oxide donor FK 409 could attenuate small-for-size graft injury in liver transplantation using small-for-size grafts. Summary Background Data: The major concern of live donor liver transplantation is small-for-size graft injury at the early phase after transplantation. Novel therapeutic strategies should be investigated. Methods: We employed a rat orthotopic liver transplantation model using small-for-size (40%) graft. FK 409 was given at 30 minutes before graft harvesting (2 mg/kg) to the donor and immediately after reperfusion (1 mg/kg) to the recipient (FK group). Graft survival, intragraft genes expression, portal hemodynamics, and hepatic ultrastructural changes were compared between the 2 groups. Results: Seven-day graft survival rates in the FK group were significantly improved compared with those of rats not receiving FK 409 (control group; 80% versus 28.6%, P = 0.018). In the FK group, portal pressure was significantly decreased within the first 60 minutes after reperfusion whereas in the control group, transient portal hypertension was observed. Intragraft expression (both mRNA and protein) of early growth response-1, endothelin-1, endothelin-1 receptor A, tumor necrosis factor-α, macrophage-inflammatory protein-2, and inducible nitric oxide synthase was significantly down-regulated accompanied with up-regulation of heme oxygenase-1, A20, interferon-γ-inducible protein-10, and interleukin-10 during the first 24 hours afier reperfusion. Hepatic ultrastructure, especially the integrity of sinusoids was well protected in the FK group. Conclusions: Low-dose FK 409 rescues small-for-size grafts in liver transplantation by attenuation of portal hypertension and amelioration of acute phase inflammatory response by down-regulation of Egr-1, together with prior induction of heat shock proteins.
Persistent Identifierhttp://hdl.handle.net/10722/49132
ISSN
2015 Impact Factor: 8.569
2015 SCImago Journal Rankings: 4.503
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMan, Ken_HK
dc.contributor.authorLee, TKen_HK
dc.contributor.authorLiang, TBen_HK
dc.contributor.authorLo, CMen_HK
dc.contributor.authorFung, PCWen_HK
dc.contributor.authorTsui, SHen_HK
dc.contributor.authorLi, XLen_HK
dc.contributor.authorNg, KTen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2008-06-12T06:35:06Z-
dc.date.available2008-06-12T06:35:06Z-
dc.date.issued2004en_HK
dc.identifier.citationAnnals Of Surgery, 2004, v. 240 n. 1, p. 159-168en_HK
dc.identifier.issn0003-4932en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49132-
dc.description.abstractObjective: To investigate whether low-dose nitric oxide donor FK 409 could attenuate small-for-size graft injury in liver transplantation using small-for-size grafts. Summary Background Data: The major concern of live donor liver transplantation is small-for-size graft injury at the early phase after transplantation. Novel therapeutic strategies should be investigated. Methods: We employed a rat orthotopic liver transplantation model using small-for-size (40%) graft. FK 409 was given at 30 minutes before graft harvesting (2 mg/kg) to the donor and immediately after reperfusion (1 mg/kg) to the recipient (FK group). Graft survival, intragraft genes expression, portal hemodynamics, and hepatic ultrastructural changes were compared between the 2 groups. Results: Seven-day graft survival rates in the FK group were significantly improved compared with those of rats not receiving FK 409 (control group; 80% versus 28.6%, P = 0.018). In the FK group, portal pressure was significantly decreased within the first 60 minutes after reperfusion whereas in the control group, transient portal hypertension was observed. Intragraft expression (both mRNA and protein) of early growth response-1, endothelin-1, endothelin-1 receptor A, tumor necrosis factor-α, macrophage-inflammatory protein-2, and inducible nitric oxide synthase was significantly down-regulated accompanied with up-regulation of heme oxygenase-1, A20, interferon-γ-inducible protein-10, and interleukin-10 during the first 24 hours afier reperfusion. Hepatic ultrastructure, especially the integrity of sinusoids was well protected in the FK group. Conclusions: Low-dose FK 409 rescues small-for-size grafts in liver transplantation by attenuation of portal hypertension and amelioration of acute phase inflammatory response by down-regulation of Egr-1, together with prior induction of heat shock proteins.en_HK
dc.format.extent388 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.annalsofsurgery.comen_HK
dc.relation.ispartofAnnals of Surgeryen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshDNA-Binding Proteins - metabolismen_HK
dc.subject.meshDown-Regulation - drug effectsen_HK
dc.subject.meshHypertension, Portal - etiology - prevention & controlen_HK
dc.subject.meshImmediate-Early Proteins - metabolismen_HK
dc.subject.meshLiver Transplantation - adverse effectsen_HK
dc.titleFK 409 ameliorates small-for-size liver graft injury by attenuation of portal hypertension and down-regulation of Egr-1 pathwayen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0003-4932&volume=240&issue=1&spage=159&epage=168&date=2004&atitle=FK409+ameliorates+small-for-size+liver+graft+injury+by+attenuation+of+portal+hypertension+and+down-regulation+of+Egr-1+pathwayen_HK
dc.identifier.emailMan, K: kwanman@hku.hken_HK
dc.identifier.emailLee, TK: tkwlee@hkucc.hku.hken_HK
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hken_HK
dc.identifier.emailNg, KT: ledodes@hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityLee, TK=rp00447en_HK
dc.identifier.authorityLo, CM=rp00412en_HK
dc.identifier.authorityNg, KT=rp01720en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1097/01.sla.0000129673.13552.c0en_HK
dc.identifier.pmid15213632-
dc.identifier.pmcidPMC1356388en_HK
dc.identifier.scopuseid_2-s2.0-3042660567en_HK
dc.identifier.hkuros90337-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-3042660567&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume240en_HK
dc.identifier.issue1en_HK
dc.identifier.spage159en_HK
dc.identifier.epage168en_HK
dc.identifier.isiWOS:000222280000023-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridLee, TK=7501439435en_HK
dc.identifier.scopusauthoridLiang, TB=7202019213en_HK
dc.identifier.scopusauthoridLo, CM=7401771672en_HK
dc.identifier.scopusauthoridFung, PCW=7101613315en_HK
dc.identifier.scopusauthoridTsui, SH=7004961357en_HK
dc.identifier.scopusauthoridLi, XL=13008588500en_HK
dc.identifier.scopusauthoridNg, KT=7403178513en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK

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