Cadmium Induces Anemia through Interdependent Progress of Hemolysis, Body Iron Accumulation, and Insufficient Erythropoietin Production in Rats

Abstract

Cadmium is a toxic heavy metal and distributed widely in the environment. In addition to damaging the liver, kidneys, and bone, cadmium causes anemia through hemolysis, iron deficiency, and insufficient erythropoietin (EPO) production (renal anemia) along with changes in iron metabolism. Here, we investigated the role of iron in the interdependent progress of three types of anemia in cadmium-injected rats fed iron-sufficient or iron-deficient diets for 1 or 3 months. Cadmium injections for 1 month induced renal anemia without renal injury. Injections for 3 months induced hemolysis, iron deficiency, and renal anemia, accompanied by hepatic and renal damage. Iron concentrations in the liver, kidney, and spleen were increased, derived from internally released iron from hemolyzed red blood cells, increased duodenal iron absorption, insufficient erythropoiesis, and hepatic ferritin overproduced by cadmium-induced interleukin-6. Therefore, the iron deficiency anemia was actually apparent. Cadmium suppressed renal EPO production through a direct effect, accumulated iron, and destruction of EPO-producing cells. Increased duodenal iron absorption could be attributed to hypertrophy of the duodenal mucosa derived from anemia. Thus, insufficient EPO production and iron accumulation are the central factors driving anemia in cadmium toxicity.

Effects of lead and cadmium co-exposure on hemoglobin in a Chinese population

“…The Cd level in our study was lower than those which may be the reason of not significant difference. Three main factors are involved in the development of Cd-induced anemia: hemolytic, iron deficiency, and renal damage (Horiguchi et al, 2007;Horiguchi et al, 2011). It has been shown that exposure to Cd could impair the production of EPO in patients with Itai-Itai disease (Horiguchi et al, 1994) and results in the marked suppression of EPO mRNA expression in the kidneys (Horiguchi et al, 1996).…”

“…It has been indicated that Cd can induce anemia due to iron deficiency through competing with iron absorption (Hamilton and Valberg, 1974). Accumulation of Cd in organs would induce excess iron accumulation, which results in EPO suppression (Horiguchi et al, 2011). In addition, Pb is taken up by the iron absorption machinery, and secondarily blocks iron through competitive inhibition.…”

Effects of Molybdenum or/and Cadmium on mRNA Expression Levels of Inflammatory Cytokines and HSPs in Duck Spleens

“…Slides were stained with hematoxylin and eosin (H&E). Afterward, pathological sections were observed using an optical microscope and photographs were taken [13].…”

Disruption of iron homeostasis and resultant health effects upon exposure to various environmental pollutants: A critical review

“…In another study by our group, we demonstrated that Cd could likely compete with ferrous iron to interact with the 5′-UTR iron response element of FPN's mRNA, affecting the translation of FPN (Sun et al, 2015). Additionally, it has been suggested that Cd may regulate hepcidin-mediated iron homeostasis by inducing the secretion of IL-6 (Horiguchi et al, 2011).…”