Possible Interaction: Glutathione and Dimethyl Fumarate

“Furthermore, DMF treatment upregulated the Nrf-2 pathway, increased NeuN+/Nrf-2+ cell number in the striatum, induced activation of manganese superoxide dismutase and heme oxygenase-1, and regulated glutathione levels.”

“ DMF modifies glutathione (GSH) levels that can induce expression of the anti-inflammatory protein HO-1 (haem oxygenase-1).”

“We explored whether the anti-inflammatory compounds Bay 11–7082, parthenolide and dimethyl fumarate (DMF) were able to completely deplete a common target ( GSH ), and to impair the function of upstream enzymes of GSH recycling and replenishment.”

“ DMF was also shown to produce an acute concentration-dependent depletion of GSH ; however, GSH levels eventually recovered and rose above baseline by 24 hours.”

“Prolonged treatment of oligodendrocytes with dimethyl fumarate induces changes in citric acid cycle intermediates, glutathione , and lipids, indicating that this compound can directly impact oligodendrocyte metabolism.”

“Therapeutical interventions that aim to increase GSH concentrations in vivo include N-acetyl cysteine; Nrf-2 activation via hyperbaric oxygen therapy; dimethyl fumarate ; phytochemicals, including curcumin, resveratrol, and cinnamon; and folate supplementation.”

“ DMF reduced intracellular GSH and induced I&kgr;B&agr; glutathionylation (I&kgr;B&agr;-SSG), which inhibited I&kgr;B&agr; degradation, NF-&kgr;B p65 nuclear entry and NF-&kgr;B/DNA binding.”

“Our data suggest that DMF inhibits NF-&kgr;B-dependent eotaxin and RANTES secretion by reduction of GSH with subsequent induction of I&kgr;B&agr;-SSG and inhibition of histone H3 phosphorylation.”

“HO-1 expression was reversed by GSH-OEt, or p38 MAPK inhibition, or HO-… siRNA, which all reversed the anti-proliferative effect of DMF.ConclusionOur data indicate that DMF inhibits ASMC proliferation by reducing the intracellular GSH level with subsequent activation of p38 MAPK and induction of HO-1.”

“In addition, DMF altered intracellular glutathione levels and thereby reduced proliferation of other cell types.”

“For these data, the role of DMF as a modulator of intracellular glutathione plays an important role.”

“Supplementation with exogenous glutathione GSH ), which is known to bind DMF, prevented both HO-1 induction as well as the anti-inflammatory effects of DMF.”