Dimethyl fumarate protects against intestinal ischemia/reperfusion lesion: Participation of Nrf2/HO-1, GSK-3ß and Wnt/ß-catenin pathway.
Biomed Pharmacother
; 134: 111130, 2021 Feb.
Article
in En
| MEDLINE
| ID: mdl-33348309
ABSTRACT
OBJECTIVE:
Dimethyl fumarate (DMFU), a known Nrf2 activator, has proven its positive effect in different organs against ischemia/reperfusion (Is/Re) injury. Nevertheless, its possible impact to modulate intestinal Is/Re-induced injury has not been previously demonstrated before. Hence, this study aimed to investigate DMFU mechanistic maneuver against intestinal Is/Re.METHODS:
To accomplish this goal, Wistar rats were allocated into four groups; Sham-operated (SOP), intestinal Is/Re (1 h/6 h), and 14 days pre-treated DMFU (15 and 25 mg/kg/day, p.o).RESULTS:
The mechanistic maneuver divulged that DMFU safeguarded the intestine partly via amplifying the expression/content of Nrf2 along with enhancing its downstream, HO-1 expression/content. In addition, DMFU lessened GSK-3ß expression/content accompanied by enriching ß-catenin expression/content. The antioxidant action was affirmed by enhancing total antioxidant capacity, besides reducing MDA, iNOS, and its by-product, NOx. The DMFU action entailed anti-inflammatory character manifested by down-regulation of expression/content NF-κB with subsequent rebating the contents of TNF-α, IL-1ß, and P-selectin, as well as MPO activity. Moreover, DMFU had anti-apoptotic nature demonstrated through enriching Bcl-2 level and diminishing that of caspase-3.CONCLUSION:
DMFU purveyed tenable novel protective mechanisms and mitigated events associated with intestinal Is/Re mischief either in the lower or the high dose partly by amending of oxidative stress and inï¬ammation through the modulation of Nrf2/HO-1, GSK-3ß, and Wnt/ß-catenin pathways.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Reperfusion Injury
/
NF-E2-Related Factor 2
/
Wnt Signaling Pathway
/
Dimethyl Fumarate
/
Glycogen Synthase Kinase 3 beta
/
Heme Oxygenase (Decyclizing)
/
Intestinal Diseases
/
Intestines
/
Anti-Inflammatory Agents
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Biomed Pharmacother
Year:
2021
Type:
Article