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Dimethyl fumarate and curcumin attenuate hepatic ischemia/reperfusion injury via Nrf2/HO-1 activation and anti-inflammatory properties.

Abstract：

BACKGROUND:Hepatic ischemia/reperfusion (I/R) injury occurs in different clinical settings as hepatic transplantation, and different types of shock. I/R injury is the main cause of hepatic damage and failure due to the production of reactive oxygen species (ROS) and inflammatory cytokines. Dimethyl fumarate (DMF), an immunomodulatory drug, activates cellularantioxidantsignaling pathways exerting cytoprotective properties. Curcumin (CUR), a natural phenolic compound, possesses antioxidant and anti-inflammatory properties. METHOD:To study potential protective effects of DMF with CUR against hepatic I/R injury in rats, animals were randomly allocated into seven groups as follows: (1) Sham; (2) DMF (25 mg/Kg, p.o); (3) CUR (400 mg/Kg, p.o.); (4) I/R; (5) DMF + I/R; (6) CUR + I/R; and combination (COM) therapy + I/R. Drugs were given for 14 days before I/R. RESULTS:Compared with I/R group, COM group showed the best amelioration in hepatic injury induced by I/R insult. This was confirmed by a significant reduction in serum ALT and AST activity with improved histopathological results when compared to every single treatment. Hepatic protection afforded by DMF was mediated by activating Nrf2/HO-1 signaling and increasing GSH and TAC contents. CUR treatment improved the inflammatory markers (TNF-α, IL-1β, Il-6 and iNOS) as well as neutrophilic infiltration assessed as MPO. Moreover, CUR potentiated Nrf2/HO-1 signaling induced by DMF with significant suppression in lipid peroxidation. CONCLUSION:We concluded that combining DMF and CUR has more efficient hepatoprotective effects against hepatic-induced IRI via potentiating antioxidant and anti-inflammatory properties mediated by Nrf2/HO-1 pathway.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Ibrahim SG,El-Emam SZ,Mohamed EA,Abd Ellah MF

doi

10.1016/j.intimp.2019.106131

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

106131

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(19)31646-7

journal_volume

80

pub_type

杂志文章

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