RGD Reference Report - Hemin induction of HO-1 protects against LPS-induced septic ileus. - Rat Genome Database

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Hemin induction of HO-1 protects against LPS-induced septic ileus.

Authors: Bortscher, S  Chang, J  Vilz, TO  Schafer, N  Sommer, N  Wehner, S  Kalff, JC  Overhaus, M 
Citation: Bortscher S, etal., J Surg Res. 2012 Dec;178(2):866-73. doi: 10.1016/j.jss.2012.07.064. Epub 2012 Aug 15.
RGD ID: 10755726
Pubmed: PMID:22921918   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jss.2012.07.064   (Journal Full-text)

BACKGROUND: Heme oxygenase (HO-1) protects against inflammation. In this study, we investigated the protective function of hemin-induced HO-1 against lipopolysaccharide (LPS)-induced ileus. METHODS: Rats received LPS intraperitoneally 24 h after intraperitoneal hemin pretreatment or placebo. We also injected zinc protoporphyrin (ZnPP, 3rd group), an inhibitor of HO-1, intraperitoneally 2 h before LPS administration. To assess intestinal muscle function, we examined muscularis strip contractility in an organ bath and measured gastrointestinal transit in vivo. We investigated inflammation within the muscularis using polymerase chain reaction (interleukin [IL]-6, inducible nitric oxide synthase (iNOS), HO-1 and IL-10) 6 and 24 h after LPS. RESULTS: Hemin significantly improved in vitro intestinal muscularis contractility (P < 0.001). In addition, hemin prevented LPS-induced dysmotility in vivo (gastrointestinal transit, geometric center: 8.39 +/- 0.33 versus 5.68 +/- 0.44; P < 0.001). In Zinc protoporphyrin (ZnPP)-treated animals, both parameters were significantly decreased compared with the hemin group. Messenger RNA expression demonstrated a significant reduction in IL-6 (6 h, hemin: 127.6 +/- 36.7 versus LPS: 14,431 +/- 5407; 24 h: 1.58 +/- 0.39 versus 11.15 +/- 2.59; P < 0.01) and iNOS (6 h: 2516 +/- 985 versus 50,771 +/- 13,321; 24 h: 55.11 +/- 10.55 versus 257.1 +/- 43.18; P < 0.001) in hemin-treated animals. Anti-inflammatory HO-1 messenger RNA levels (6 h, hemin: 116.3 +/- 18.55 versus LPS: 26.02 +/- 3.64; 24 h: 18.46 +/- 2.69 versus 2.80 +/- 0.32; P < 0.001) were increased. There was no significant difference in IL-10 levels at 6 and 24 h. ZnPP reversed the anti-inflammatory hemin effects. CONCLUSIONS: Hemin induction of HO-1 diminishes LPS-induced sepsis. Heme oxygenase-1 has a central role in preventing sepsis-induced ileus. This benefit is reversed by HO-1 inhibition with ZnPP.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ileus treatmentISOHmox1 (Rattus norvegicus)10755726; 10755726associated with SepsisRGD 
ileus treatmentIEP 10755726associated with SepsisRGD 

Objects Annotated

Genes (Rattus norvegicus)
Hmox1  (heme oxygenase 1)

Genes (Mus musculus)
Hmox1  (heme oxygenase 1)

Genes (Homo sapiens)
HMOX1  (heme oxygenase 1)


Additional Information