RGD Reference Report - Inhibition of classical complement activation attenuates liver ischaemia and reperfusion injury in a rat model. - Rat Genome Database

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Inhibition of classical complement activation attenuates liver ischaemia and reperfusion injury in a rat model.

Authors: Heijnen, BH  Straatsburg, IH  Padilla, ND  Van Mierlo, GJ  Hack, CE  Van Gulik, TM 
Citation: Heijnen BH, etal., Clin Exp Immunol. 2006 Jan;143(1):15-23.
RGD ID: 1580273
Pubmed: PMID:16367929   (View Abstract at PubMed)
PMCID: PMC1809558   (View Article at PubMed Central)
DOI: DOI:10.1111/j.1365-2249.2005.02958.x   (Journal Full-text)

Activation of the complement system contributes to the pathogenesis of ischaemia/reperfusion (I/R) injury. We evaluated inhibition of the classical pathway of complement using C1-inhibitor (C1-inh) in a model of 70% partial liver I/R injury in male Wistar rats (n = 35). C1-inh was administered at 100, 200 or 400 IU/kg bodyweight, 5 min before 60 min ischaemia (pre-I) or 5 min before 24 h reperfusion (end-I). One hundred IU/kg bodyweight significantly reduced the increase of plasma levels of activated C4 as compared to albumin-treated control rats and attenuated the increase of alanine aminotransferase (ALT). These effects were not better with higher doses of C1-inh. Administration of C1-inh pre-I resulted in lower ALT levels and higher bile secretion after 24 h of reperfusion than administration at end-I. Immunohistochemical assessment indicated that activated C3, the membrane attack complex C5b9 and C-reactive protein (CRP) colocalized in hepatocytes within midzonal areas, suggesting CRP is a mediator of I/R-induced, classical complement activation in rats. Pre-ischaemic administration of C1-inh is an effective pharmacological intervention to protect against liver I/R injury.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SERPING1HumanLiver Reperfusion Injury treatmentIDA  RGD 
Serping1RatLiver Reperfusion Injury treatmentISORGD:1344082 RGD 
Serping1MouseLiver Reperfusion Injury treatmentISORGD:1344082 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CrpRatcomplement activation, classical pathway  IMP  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
C3Ratclassical complement pathway  IMP  RGD 
C3Humanclassical complement pathway  ISORGD:2232 RGD 
C3Mouseclassical complement pathway  ISORGD:2232 RGD 
C4aRatclassical complement pathway  IMP  RGD 
C4bMouseclassical complement pathway  ISORGD:620005 RGD 
CRPHumanclassical complement pathway  ISORGD:2411 RGD 
CrpRatclassical complement pathway  IMP  RGD 
CrpMouseclassical complement pathway  ISORGD:2411 RGD 
Objects Annotated

Genes (Rattus norvegicus)
C3  (complement C3)
C4a  (complement C4A)
Crp  (C-reactive protein)
Serping1  (serpin family G member 1)

Genes (Mus musculus)
C3  (complement component 3)
C4b  (complement C4B (Chido blood group))
Crp  (C-reactive protein, pentraxin-related)
Serping1  (serine (or cysteine) peptidase inhibitor, clade G, member 1)

Genes (Homo sapiens)
C3  (complement C3)
CRP  (C-reactive protein)
SERPING1  (serpin family G member 1)


Additional Information