title: The fibrin-derived peptide bβ15-42 attenuates liver damage in a rat model of liver ischemia/reperfusion injury.
abstract: The inflammatory response after liver ischemia/reperfusion (I/R) contributes to increased risk of liver failure after liver surgery. Strategies aimed to preventing inflammation could be beneficial in reducing liver I/R injury. Recent studies have demonstrated that peptide Bβ15-42 is able to decrease the injury of I/R in heart and kidney by inhibition of leukocyte migration and preserving endothelial barrier function. Prompted by these results, we hypothesized that Bβ15-42 could also possess anti-inflammatory abilities to protect from or reduce hepatic I/R injury. Therefore, in this study, we aimed to evaluate the effects of Bβ15-42 in a model of liver I/R injury in rats. Rats were treated with Bβ15-42 at initiation of reperfusion and 2 h thereafter. Rats were killed at 0.5, 6, 24, and 48 h after reperfusion. Hepatic mRNA levels of fibrinogen-α (Fgα), Fgβ, Fgγ were significantly increased after I/R. Treatment with Fg-derived Bβ15-42 ameliorated liver I/R injury, as indicated by lower serum aminotransferase levels and fewer I/R-associated histopathologic changes. Bβ15-42 treatment decreased leukocyte infiltration and expression of hepatic inflammatory cytokines. Moreover, Bβ15-42 significantly reduced high-mobility group box 1 release and altered mitogen-activated protein kinase activation. In conclusion, Bβ15-42 treatment protected against liver warm I/R injury. The mechanism of protective action of Bβ15-42 seemed to involve its ability to reduce hepatic inflammatory response through preventing high-mobility group box 1 release and altering mitogen-activated protein kinase activation.
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Anding.liu@uk-essen.de
authors.forename: Anding
authors.initials: A
authors.lastname: Liu
authors.forename: Haoshu
authors.initials: H
authors.lastname: Fang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Hua
authors.initials: H
authors.lastname: Fan
authors.forename: Shenpei
authors.initials: S
authors.lastname: Liu
authors.forename: Olaf
authors.initials: O
authors.lastname: Dirsch
authors.forename: Uta
authors.initials: U
authors.lastname: Dahmen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002317:Cardiovascular Agents / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000378:metabolism; D008099:Liver / Q000098:blood supply*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D000637:Transaminases / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002317:Cardiovascular Agents; D016207:Cytokines; D005338:Fibrin Fibrinogen Degradation Products; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D010446:Peptide Fragments; C033786:fibrinogen Bbeta (15-42); D000637:Transaminases