Differential Regulation of Slc40a1, Fth1, and Hmox1 by Deferasirox in Splenic Iron Overload

Iron overload, often arising from repeated transfusions in thalassemia major, disrupts iron homeostasis and induces oxidative stress. Deferasirox is a widely used oral chelator, yet its effects on splenic iron-regulatory gene expression remain unclear. This study investigated the impact of deferasirox on ferritin heavy chain (Fth1), ferroportin (Slc40a1), and heme oxygenase-1 (Hmox1) expression in a rat model of splenic iron overload. Eighteen male Wistar rats were randomly assigned into three groups (n = 6 each): normal (N), iron dextran-induced overload without treatment (KN), and iron overload treated with deferasirox (KP). Gene expression was quantified by real-time PCR using the 2−ΔΔCT (Livak) method, with statistical analysis performed via one-way ANOVA and Tukey’s post hoc test. Iron overload significantly upregulated Fth1 (2.26-fold) and Slc40a1 (1.72-fold) versus controls (p < 0.05). Deferasirox treatment reduced Fth1 (3.28-fold decrease) and Slc40a1 (1.15-fold reduction) relative to untreated overload, though not significantly (p > 0.05). In contrast, Hmox1 expression markedly increased (55.25-fold, p < 0.05) following deferasirox administration. These results indicate that deferasirox selectively modulates splenic iron-regulatory genes, suggesting both chelation and adaptive stress-response mechanisms, thereby supporting its therapeutic role in managing iron overload.