Dimethyl Fumarate Reduces Inflammatory Responses in Experimental Colitis

Abstract

DMF treatment reduces the degree of colitis caused by DNBS. We propose that DMF treatment may be useful in the treatment of inflammatory bowel disease.

Hemin reduces postoperative ileus in a heme oxygenase 1‐dependent manner while dimethyl fumarate does without heme oxygenase 1‐induction

“…But only the dosage of 100 mg kg ‐1 of DMF resulted in a significant increase in colonic nuclear Nrf2 protein levels, which regulate the expression of HO‐1; whereas both doses were able to significantly reduce colonic NF‐κB p65 activity. Taken together, these data might indicate that in vivo, induction of HO‐1 by DMF requires a higher dose and/or longer treatment duration; whereas inhibition of NF‐κB might already occur at a lower dose and/or shorter treatment duration . The NF‐κB inhibiting effect of DMF was also reported by Gillard et al; in their study DMF inhibited nuclear translocation of NF‐κB p65 in U‐2 OS cells and inhibited NF‐κB‐driven cytokine production in murine splenocytes, and doing so in an Nrf2‐independent manner .…”

“…Hence, we opted for a single administration of 30 mg kg ‐1 DMF ip at 24 hours before IM, based on the study of Kunze et al in which they tested the effect of DMF on focal cerebral ischemia in mice and illustrated that the greatest induction in HO‐1 gene expression occurs after 1 day of treatment with 15 mg kg ‐1 DMF ip twice a day . We also included 100 mg kg ‐1 DMF ig because of its proven beneficial effect in an experimental model of colitis, which is, similar to POI, also characterized by inflammation of the gastrointestinal tract . In our study, we have shown that pretreatment with both 30 mg kg ‐1 DMF ip or 100 mg kg ‐1 DMF ig had a protective effect on POI in mice, equaling that of hemin.…”

“…Group III and IV received DMF, respectively, ip (30 mg kg ‐1 ) or ig (100 mg kg ‐1 ) at 24 hours before the surgical procedure. The dose/schedule selection was based on literature . Mice were killed at 3, 6, or 24 hours after surgery.…”

“…In an in vitro study in BV2 microglial cells, DMF showed one of the best HO‐1 inducing/cytotoxicity profiles among the 56 compounds tested . In murine colitis, oral administration of DMF resulted in inhibition of NF‐κB translocation and reduction of inflammatory parameters . The aim of the actual study was to investigate the influence of DMF and hemin on murine POI, and the involvement of HO‐1; preliminary accounts of the results have been presented…”

The Neuroprotective Effect of Dimethyl Fumarate in an MPTP-Mouse Model of Parkinson's Disease: Involvement of Reactive Oxygen Species/Nuclear Factor-κB/Nuclear Transcription Factor Related to NF-E2

“…and then decapitated with large bandage scissors; their brains were harvested, sectioned, and processed. The dose of MPTP (20 mg/kg) used was based on previous in vivo studies (22), whereas doses of DMF were based on our previous colitis study (13) as well as on prior dose-response and timecourse studies in our laboratory. Experimental data regarding groups 2, 3, and 4 are related only to histological evaluation, as DMF administration did not result in either toxicity or improvement in comparison to sham controls (revised Fig.…”