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Thiazolidinones reduce iron overload
156 and 165 were selected for further investigation in the subsequent experiments.
Compounds 93, 156 and 165 altered iron distribution in wildtype mice
As delineated above, after screening, three compounds, 93, 156 and 165, were selected for detailed examination. To determine whether these compounds altered iron dis-
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tribution in vivo, we measured the time course of hepatic hepcidin and concomitant changes of iron levels in mice challenged by compounds 93, 156 and 165. The experi- mental design for the experiments with Wt mice is depict- ed in Figure 2A. For a short-term study, mice received a single intraperitoneal injection of each compound at a dose of 30 mg/kg body weight, and were then sacrificed at 6, 24, 48, 72 and 96 h. Compounds 93, 156 and 165 rap-
Figure 2. Testing thiazolidinone derivatives for their effects on hepatic hepcidin in wildtype mice. (A) Diagram of the experimental design. (B) Hepatic hepcidin mRNA, (C) serum hepcidin, (D) serum iron and (E) splenic iron in 8-week old Balb/C wildtype (Wt) mice treated with compounds 93, 156 and 165 at a dose of 30 mg/kg body weight at various time points (n=4-6). (F) Splenic iron shown by Perls Prussian blue staining (blue areas evidenced by arrows) of mice treated with compounds 93, 156 and 165 at a dose of 30 mg/kg body weight for 24 h and 12 days. Original magnification, ×200. *P<0.05; #P<0.001, compared to untreated control (Ctrl).
haematologica | 2019; 104(9)
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