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  • Title: Augmented NRF2 activation protects adult sickle mice from lethal acute chest syndrome.
    Author: Ghosh S, Hazra R, Ihunnah CA, Weidert F, Flage B, Ofori-Acquah SF.
    Journal: Br J Haematol; 2018 Jul; 182(2):271-275. PubMed ID: 29923176.
    Abstract:
    Acute chest syndrome (ACS) mortality in sickle cell disease (SCD) rises sharply in young adult patients and mechanism-based prophylaxis is lacking. In SCD, haem oxygenase-1 (HO-1) declines with age and ACS is associated with low HO-1. To test if enhanced HO-1 can reduce ACS mortality, young SCD mice were treated with D3T (3H-1,2-dithiole-3-thione), an activator of nuclear-factor erythroid 2 like 2, which controls HO-1 expression, for 3 months. Following haem-induced ACS, all vehicle-treated mice succumbed to severe lung injury, while D3T-treated mice had significantly improved survival. Blocking HO-1 activity abrogated the D3T effect. Thus HO-1 may be targeted to reduce ACS severity in adult patients.
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