Diverse effects of chronic cobalt supplementation on iron metabolism during erythropoiesis

Cobalt (Co) is an essential trace element and its cellular uptake occurs in a similar to iron (Fe) profile. The aim was to assess the alterations in iron and Fe regulatory proteins concentrations - transferrin receptor 1 (TfR1), hepcidin and ferritin, and their effect on erythrocyte count (RBCs) in mice following chronic exposure to cobalt chloride (CoCl ₂ ). Pregnant ICR mice were subjected to 125 mg/kg body weight CoCl ₂ x6H ₂ O daily 2–3 days prior delivery and treatment continued 90 days after birth. CoCl ₂ was administrated with drinking water. Pups were sacrificed on postnatal days 18, 30, 45, 60 and 90. Exposure to CoCl ₂ induced significant accumulation of Co ions in blood sera and RBCs. During long-term exposure the most Co was accumulated in the serum after 30 days of exposure and decreased by day 90 of dosing indicating that serum Co concentration is a reliable marker for recent exposure. Hemoglobin content increased in a time-dependent manner. Co administration significantly elevated serum Fe but decreased it in RBCs. Exposure to Co stimulated Fe storage, enhancing hepcidin production and ferritin concentrations, and reducing TfR1 expression. Chronic exposure to CoCl ₂ resulted in a lower Fe content of mature mice compared to immature suggesting stimulated Fe release as a possible survival mechanism to counteract the toxic effects of Fe overload.