Page 97 - 2019_09-HaematologicaMondo-web

Thiazolidinones reduce iron overload
mulation in spleens compared to these processes in nor- mal mice (P<0.05) (Online Supplementary Figure S11).
Hfe-/- mice (5 weeks old) on a normal diet were treated with compounds 93, 156 and 165 at a dose of 10 mg/kg body weight every other day, and were sacrificed 2 weeks later (Figure 5B). Serum hepcidin was increased 2 fold after
AB
administration of compound 93 and 2.3 fold after admin- istration of compounds 156 and 165, relative to the levels in untreated Hfe-/- mice (P<0.05) (Figure 5C). As an expect- ed consequence of increased hepcidin, serum iron and hepatic iron were reduced (P<0.05) (Figure 5D, E), with a concomitant increase of splenic iron (P<0.05) (Online
CDE
F
Figure 5. Treatment with compounds 93, 156 and 165 redistributed iron in Hfe-/- mice. (A) Serum hepcidin in wildtype (Wt) 129S and Hfe-/- mice at different ages. (B) The experimental scheme. Changes of (C) serum hepcidin, (D) serum iron and (E) hepatic iron in Hfe-/- mice after treatment with compounds 93, 156 and 165 at a dose of 10 mg/kg body weight for 2 weeks (n=4-6). (F) Perls Prussian blue staining of liver and spleen (in blue, indicated by arrows) and 3'-diaminobenzidine- enhanced Perls Prussion staining of duodenum (in brown) of 5-week-old Hfe-/- mice treated with compounds 93, 156 and 165 at a dose of 10 mg/kg body weight every other day for 2 weeks. Original magnification, ×200 for spleen sections; ×400 for liver and duodenum sections. *P<0.05; #P<0.001, compared to the untreated, control (Ctrl) Hfe-/- mice.
haematologica | 2019; 104(9)
1775