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
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Liver Reperfusion Injury treatmentIDA 1580273 RGD 
Liver Reperfusion Injury treatmentISOSERPING1 (Homo sapiens)1580273; 1580273 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
complement activation, classical pathway  IMP 1580273 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

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