Related Experiment Video
Updated: Jan 24, 2026
Bioluminescence Imaging of Heme Oxygenase-1 Upregulation in the Gua Sha Procedure
Published on: August 28, 2009
Hemin reduces postoperative ileus in a heme oxygenase 1-dependent manner while dimethyl fumarate does without heme
Jonas Van Dingenen1, Leen Pieters2, Elien Van Nuffel3,4
1Department of Basic and Applied Medical Sciences, Faculty of Medicine & Health Sciences, Ghent University, Ghent, Belgium.
Background:
Postoperative ileus (POI), the impairment of gastrointestinal motility after abdominal surgery, is mainly due to intestinal muscular inflammation. Carbon monoxide (CO)-releasing compounds were shown to exert an anti-inflammatory effect in murine POI partially through induction of heme oxygenase-1 (HO-1). The influence of hemin and dimethyl fumarate (DMF), currently used for multiple sclerosis (MS), was therefore tested in murine POI.
Methods:
C57BL/6J mice were anesthetized and after laparotomy, POI was induced via intestinal manipulation (IM). Animals were treated with either 30 mg kg-1 hemin intraperitoneally (ip), 30 mg kg-1 DMF ip, or 100 mg kg-1 intragastrically (ig) 24 hours before IM. Intestinal transit was assessed 24 hours postoperatively and mucosa-free muscularis or whole segments of the small intestine were stored for later analysis. Intestinal HO-1 protein expression was studied at 6, 12, and 24 hours after administration of hemin or DMF in non-manipulated mice.
Key Results:
Pretreatment with hemin and DMF, both ig and ip, prevented the delayed transit seen after IM. Concomitantly, both hemin and DMF significantly reduced the increased interleukin-6 levels and the elevated leukocyte infiltration in the muscularis. Hemin but not DMF caused a significant increase in intestinal HO-1 protein expression and co-administration of the HO-1 inhibitor chromium mesoporphyrin abolished the protective effects of hemin on POI; DMF reduced the IM-induced activation of NF-κB and ERK 1/2.
Conclusions And Inferences:
Both hemin and DMF improve the delayed transit and inflammation seen in murine POI, but only hemin does so in a HO-1-dependent manner.
Insights
Hemin and dimethyl fumarate (DMF) treat postoperative ileus (POI) in mice by reducing inflammation. Hemin
Area of Science:
- Gastroenterology
- Pharmacology
- Surgical Research
Background:
- Postoperative ileus (POI) is a common complication of abdominal surgery, characterized by impaired gastrointestinal motility due to intestinal inflammation.
- Carbon monoxide (CO)-releasing molecules have demonstrated anti-inflammatory properties in murine POI models, partly by inducing heme oxygenase-1 (HO-1).
- Hemin and dimethyl fumarate (DMF), a drug used for multiple sclerosis, were investigated for their potential to treat POI.
Purpose of the Study:
- To evaluate the efficacy of hemin and DMF in a murine model of postoperative ileus.
- To investigate the underlying mechanisms, including the role of heme oxygenase-1 (HO-1), NF-κB, and ERK 1/2 signaling pathways.
Main Methods:
- Postoperative ileus was induced in C57BL/6J mice via intestinal manipulation (IM).
- Mice were pretreated with hemin or DMF via intraperitoneal (ip) or intragastric (ig) administration 24 hours before IM.
- Intestinal transit, interleukin-6 levels, leukocyte infiltration, HO-1 protein expression, and activation of NF-κB and ERK 1/2 were assessed.
Main Results:
- Both hemin and DMF significantly improved delayed intestinal transit and reduced inflammation (interleukin-6 levels, leukocyte infiltration) in POI mice.
- Hemin treatment led to a significant increase in intestinal HO-1 protein expression, and this effect was abolished by a HO-1 inhibitor.
- DMF reduced the activation of NF-κB and ERK 1/2 signaling pathways.
Conclusions:
- Hemin and DMF are effective in improving delayed transit and reducing inflammation in a murine model of POI.
- Hemin exerts its protective effects through a mechanism dependent on HO-1 induction.
- DMF ameliorates POI by modulating NF-κB and ERK 1/2 signaling pathways, independent of HO-1.
Related Concept Videos
02:15SN1 Reaction: Stereochemistry
In the first step of an SN1 reaction, the bond between the electrophilic carbon and the leaving group ionizes to generate the carbocation intermediate. The second step of the mechanism is the nucleophilic attack.
In the formed carbocation, the positively charged carbon is sp2 hybridized with a trigonal planar geometry. As all the three substituents lie on the same plane, a plane of symmetry for the...
02:05SN1 Reaction: Kinetics
However, Sir Christopher Ingold and Edward D. Hughes, who studied the kinetics of various nucleophilic substitution reactions, noticed that a tertiary alkyl halide does undergo a nucleophilic substitution reaction in the presence of a weak nucleophile. While studying the substitution...
02:25SN1 Reaction: Mechanism
Firstly, the haloalkane ionizes to generate a carbocation intermediate and a halide ion. This heterolytic cleavage is highly endothermic with large activation energy. The ionization of the substrate, facilitated by a...
02:42Acidity of 1-Alkynes
The acidic strength of hydrocarbons follows the order: Alkynes > Alkenes > Alkanes. The strength of an acid is commonly expressed in units of pKa — the lower the pKa, the stronger the acid. Among the hydrocarbons, terminal alkynes have lower pKa values and are, therefore, more acidic. For example, the pKa values for ethane, ethene, and acetylene are 51, 44, and 25, respectively, as shown here.
02:27Predicting Products: SN1 vs. SN2
With increased substitution on the alkyl halide,...
01:28Preparation of 1° Amines: Gabriel Synthesis
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...