The Impact of Sodium Selenite and Seleno-L-Methionine on Stress Erythropoiesis in a Murine Model of Hemolytic Anemia

Background: Selenium (Se) is an essential trace element that exerts most biological activities through selenoproteins. Dietary selenium is a key regulator of red cell homeostasis and stress erythropoiesis. However, it is unknown whether the form and increasing doses of Se supplementation in the diet impact stress erythropoiesis under anemic conditions.

Objectives: If inorganic (sodium selenite; Na₂SeO₃) or organic [seleno-L-methionine (Se-Met)] forms of Se in different amounts (deficient, adequate, supplemented, and supranutritional) support stress erythropoiesis in anemic mice.

Methods: Three-wk-old male C57BL/6 mice were subjected to graded amounts of Se in the form of <0.01 mg/kg Se [Se-deficiency (Se-D)], 0.1 mg/kg Na₂SeO₃ (adequacy), 0.4 mg/kg Na₂SeO₃ (supplemented), 3 mg/kg Na₂SeO₃ (supranutritional), 0.4 mg/kg Se-Met (supplemented), or 3 mg/kg Se-Met (supranutritional), for 10-12 wk before intraperitoneal phenylhydrazine administration to induce hemolytic anemia. Following 3 d of phenylhydrazine injection, spleen and blood samples were used to assess the impact of form and graded amounts of Se in the diet on stress erythropoiesis.

Results: Phenotypic parameters showed that supplementing the diet with Se in the form of Na₂SeO₃ or Se-Met alleviated hemolytic anemia and promoted stress erythropoiesis by supporting the formation of erythroblastic islands. Se-Met at 0.4 mg/kg enhanced erythroid progenitor differentiation by 2-fold compared with Se-D, while Na₂SeO₃ at 0.4 mg/kg and 3 mg/kg significantly (P < 0.05) aided monocyte recruitment and macrophage differentiation within erythroblastic islands. Additionally, 3 mg/kg of Se-Met triggered a stronger inflammatory response than the same dose of Na₂SeO_3. CONCLUSIONS: While both Se-Met and Na₂SeO₃ effectively aid in stress erythropoiesis, Na₂SeO₃ supplementation effectively support stress erythropoiesis with a minimal inflammatory response, while Se-Met at supranutritional dosage lead to increased inflammation despite its support for stress erythropoiesis. These results indicate diverse mechanisms of action of Se on the alleviation of anemia by stress erythropoiesis, which should be considered for further studies to complement existing therapies.