Control of Oxidative Stress and Inflammation in Sickle Cell Disease with the Nrf2 Activator Dimethyl Fumarate.

ABSTRACT:

Aims

Heme derived from hemolysis is pro-oxidative and proinflammatory and promotes vaso-occlusion in murine models of sickle cell disease (SCD), suggesting that enhanced detoxification of heme may be beneficial. Nuclear factor erythroid-2-related factor-2 (Nrf2) transcription pathway is the principal cellular defense system responding to pro-oxidative and proinflammatory stress. Dimethyl fumarate (DMF), a drug approved for treatment of multiple sclerosis, provides neuroprotection by activating Nrf2-responsive genes. We hypothesized that induction of Nrf2 with DMF would be beneficial in murine SCD models.

Results

DMF (30 mg/kg/day) or vehicle (0.08% methyl cellulose) was administered for 3-7 days to NY1DD and HbSS-Townes SCD mice. Vaso-occlusion, a hallmark of SCD, measured i

SUBMITTER: Belcher JD 

PROVIDER: S-EPMC5421647 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature