Chronic DMF administration decreases hepatic necrosis in livers of sickle mice. HbSS-Townes (n = 4/group) sickle mice were treated with oral DMF (∼30 mg/kg/day) or vehicle in drinking water for 24 weeks, beginning at 4 weeks of age. Liver sections were stained with hematoxylin and eosin. (A) “Acute” infarcts were defined as eosinophilic areas of coagulative necrosis without significant reactive cellular infiltrates, reflecting relatively recent acute or subacute necrosis. (B) “Chronic” infarcts were somewhat less clearly delineated and comprised infiltrates of mononuclear cells (lymphocytes and macrophages) along with variable degrees of fibroplasia and fibrosis. (C) Areas of acute and chronic hepatic necrosis were measured, combined, and averaged for each liver. Each box plot represents the minimum box plot represent the minimum, first quartile, median, third quartile, and maximum. *p = 0.039 for DMF versus vehicle. (D) Hepatic mRNA levels of proinflammatory cytokines IL-6, IL-1β, and IL-18 are expressed relative to 18S rRNA. *p < 0.05 for DMF versus vehicle. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars