Fig. 2

Niacin supplement rescues KPT-9274-induced acute kidney toxicity. A Gross images (top panel) and H&E staining (middle and bottom panels) of renal lesions in NSG mice which received KPT-9274 treatment for 3 weeks. Mice treated with KPT-9274 show marked pitting on the renal surface, which corresponds histologically to the areas of tubular collapse and fibrosis. The pitting is ameliorated by niacin treatment. B Percent areas with renal injury are quantified for each treatment group. C Serum levels of creatinine and BUN are measured in treated NSG mice. Levels across all groups are within normal limits with a slight increase in creatinine levels in KPT-9274-treated mice. D Measurement of erythropoietin in the serum of KPT-9274 + niacin-, KPT-9274-, niacin-, and vehicle-treated NSG mice after 3 weeks of treatment.*p-value < 0.05. E KPT-9274 maintains potency toward AML cells in the presence of niacin. OCI-AML3 cells were treated with vehicle, 0.25 µM KPT-9274 or 2.5 µM KPT-9274 in the presence of normal media, niacin or NAD + for 48 h before being subject to Annexin V/PI staining and flow cytometry analysis. Data from three independent experiments are expressed as mean ± SEM. *p-value < 0.05; ****p-value < 0.0001