A potent and highly selective FXa inhibitor, edoxaban tosylate monohydrate (Ex) (MedChem Express, Monmouth Junction, NJ), an orally active prodrug of edoxaban, was administered to mice through oral gavage. Ex was dissolved in 0.5 w/v% methylcelluloses 400 solution (0.5% MC; FUJIFILM Wako Pure Chemical Industries, Ltd., Osaka, Japan) [29 (link)]. In our model, Ex was administered orally to mice because it must undergo chemical conversion by metabolic processes through oral intake for activation. Previously, sufficient anticoagulant effects on mice were observed at 60 minutes after oral administration of 10 mg/kg Ex [30 (link)], and renal protective effects for diabetic nephropathy mice model were observed with 50 mg/kg/day [31 (link),32 (link)]. Following these reports, to examine the effect of Ex treatment in our mice hepatic IRI model, based on serum alanine transaminase (ALT) levels at 4 hours after reperfusion, we set the doses of Ex as 3, 10, 30, and 50 mg/kg, and administered them orally 60 minutes before ischemia (n = 5 per group). A dose of 50 mg/kg had a significant effect: 1,008 [800–1,474] IU/L in controls (Vehicle) vs. 89 [35–242] IU/L in the edoxaban group (p = 0.05) (S1 Fig ). Accordingly, we decided to administer 50 mg/kg of Ex.
Free full text: Click here
