Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. 
Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. What was studied?
This original toxicology study probed cadmium-induced anemia mechanisms by testing how cadmium (Cd) exposure drives anemia via hemolysis, altered iron handling, and suppressed erythropoietin (EPO) in rats on iron-sufficient versus iron-deficient diets. The authors integrated hematology, histopathology, organ metal burdens, radiolabeled iron kinetics, and expression of iron-regulatory genes to resolve whether iron deficiency, iron accumulation, and EPO suppression act independently or interdependently in cadmium toxicity.
Who was studied?
Female Wistar rats received subcutaneous CdCl₂ (2 mg/kg) or saline twice weekly for one or three months while consuming either a basal diet (≈60 ppm Fe) or a low-iron diet (10–20 ppm Fe). Hematologic indices, plasma iron, EPO, ferritin, and TIBC, together with urinary NAG, glucose, transferrin, and hemoglobin, were measured; organs were examined histologically and for metal content, and iron flux was traced using oral ^59Fe. This design allowed discrimination between diet-induced iron deficiency and cadmium-induced anemia mechanisms, capturing early functional EPO suppression at one month and combined hemolytic, renal, and apparent iron-deficiency features at three months
Most important findings
| Critical Point | Details |
|---|---|
| Tripartite Anemia Mechanism | Cadmium exposure induces a complex anemia involving hemolysis (evidenced by deformed RBCs and splenomegaly), apparent iron deficiency (low plasma iron despite high organ iron), and renal anemia (insufficient EPO production due to direct suppression and renal damage). |
| Systemic Iron Accumulation | Contrary to simple deficiency, cadmium caused significant iron accumulation in the liver, kidney, and spleen. This was driven by internal iron release from hemolyzed RBCs, increased duodenal iron absorption from mucosal hypertrophy, and hepatic ferritin overproduction induced by Cd-stimulated IL-6. |
| EPO Suppression Pathways | Renal EPO production was suppressed both functionally (directly by Cd and indirectly via iron accumulation disrupting HIF-α) and pathologically (through destruction of EPO-producing cells from advancing renal tubular injury). |
| Altered Iron Homeostasis | Cadmium dysregulated iron metabolism. It initially suppressed the iron-regulatory hormone hepcidin, but long-term exposure led to IL-6-driven hepcidin induction. It also decreased ferroportin1 in splenic macrophages, trapping recycled iron, and downregulated renal DMT1, contributing to urinary iron loss. |
| Apparent Iron Deficiency | The study identified a state of “apparent iron deficiency anemia” where classic hematological signs of deficiency (low plasma iron, high TIBC) coexist with elevated total body iron stores, rendering the iron unavailable for effective erythropoiesis. |
Key implications
The primary regulatory impact is the need to recognize that cadmium exposure causes a complex anemia not remedied by simple iron supplementation. Certification requirements should mandate testing for body iron status and renal function, not just hemoglobin. For industry applications, this underscores risks in sectors with cadmium exposure where anemia is present. A critical research gap is developing therapies that address iron sequestration and EPO suppression. Practical recommendations include comprehensive health monitoring for cadmium-exposed workers that includes EPO levels and ferritin, alongside cadmium biomonitoring.
Citation
Horiguchi H, Oguma E, Kayama F. Cadmium induces anemia through interdependent progress of hemolysis, body iron accumulation, and insufficient erythropoietin production in rats. Toxicol Sci. 2011. doi:10.1093/toxsci/kfr178
Cadmium is a persistent heavy metal that accumulates in kidneys and bones. Dietary sources include cereals, cocoa, shellfish and vegetables, while smokers and industrial workers receive higher exposures. Studies link cadmium to kidney dysfunction, bone fractures and cancer.
