The DMF-induced decrease in cellular GSH levels as well as cell viability and increase in reactive oxygen species (ROS) were inhibited by co-treatment with GSH and N-acetylcysteine (NAC) in CT26 cells.

Here, we found that DMF indeed induces glutathione reductase (GSR), a homodimeric flavoprotein that catalyzes GSSG reduction to GSH by using NADPH as a reducing cofactor.

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. In contrast, MEF did not cause acute reductions in GSH, but did produce an increase by 24 hours.

DMF modulates ROS and GSH concentrations in non-tumorigenic cells differently from that of cancer cells. As previously reported, 100 μM DMF induced GSH depletion and increased oxidative stress in a time-dependent manner in the two cancer cell lines, MiaPaca-2 and SW480 (Figure 4B–4C).

Mar 18, 2024 · Dimethyl fumarate (DMF) is an anti-inflammatory and immunoregulatory drug used to treat patients with multiple sclerosis and psoriasis in which it blocks aberrant NF-κB pathways and impacts the...

Several genes related to GSH synthesis were upregulated at the same time, suggesting that a potential compensatory response may occur to reduce oxidative burst following DMF treatment. Our results suggest that DMF-mediated oxidative stress alters a range of cell signaling pathways, including MYC, leading to cell cycle arrest and a defective ...

6 days ago · Moreover, DMF ameliorated cellular reactive oxygen species (ROS) (Fig. S4a, b) and increased malondialdehyde (MDA), superoxide dismutase (SOD), and Glutathione (GSH) levels (Fig. S4h–j). These ...

Jan 23, 2015 · Here, we show that the accumulation of fumarate caused by the inactivation of FH leads to oxidative stress that is mediated by the formation of succinicGSH, a covalent adduct between fumarate and...

Nov 22, 2024 · Our findings indicate that DMF increases levels of glutathione (GSH), glutamate cysteine ligase modifier subunit (GCLM), and nuclear Nrf2 in SH-SY5Y cells. Importantly, DMF pretreatment significantly reduced the accumulation of MG-H1-modified proteins.

DMF’s immunomodulatory and antioxidative effects rely on its regulation of several pathways, among which the Keap1/Nrf2/ARE and NF-κB pathways, the modulation of GSH levels, its agonism of HCAR2 and its effects on the autophagic system.