The impact of sodium selenite and seleno-L-methionine on stress erythropoiesis in a murine model of hemolytic anemia

Abstract

BackgroundSelenium (Se) is an essential trace element that exerts most biological activities through selenoproteins. Dietary selenium (Se) is a key regulator of red cell homeostasis and stress erythropoiesis. However, it is unknown if the form and increasing doses of Se supplementation in the diet impacts stress erythropoiesis under anemic conditions. ObjectiveIf inorganic (sodium selenite; Na2SeO3) or organic (seleno-L-methionine, Se-Met) forms of Se within different concentrations (deficient, adequate, supplemented, and supranutritional) support stress erythropoiesis in anemic mice. MethodsThree-week-old male C57BL/6 mice were subjected to graded levels of Se in the form of <0.01 ppm Se (Se-deficiency; Se-D), 0.1ppm Na2SeO3 (adequacy), 0.4ppm Na2SeO3 (supplemented), 3ppm Na2SeO3 (supranutritional), 0.4ppm Se-Met (supplemented), or 3ppm Se-Met (supranutritional), for 10-12 weeks prior to intra-peritoneal phenylhydrazine (PHZ) administration to induce hemolytic anemia. Following three days post-PHZ injection, spleen and blood samples were used to assess the impact of form and graded levels of Se in the diet on stress erythropoiesis. ResultsPhenotypic 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 (EBIs). Se-Met at 0.4 ppm enhanced erythroid progenitor differentiation, while Na2SeO3 at 0.4 ppm and 3 ppm aided monocyte recruitment and macrophage differentiation within EBIs. Additionally, 3 ppm Se-Met triggered a stronger inflammatory response than the same dose of Na2SeO3. ConclusionsWhile both Se-Met and Na2SeO3 effectively aided in stress erythropoiesis, Na2SeO3 supplementation effectively supported stress erythropoiesis with a minimal inflammatory response, while Se-Met at supranutritional dosage led 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.