Vitamin A modulates inflammatory status,
iron metabolism and erythropoiesis. Given that these factors modulate the expression of the
hormone hepcidin (Hamp), we investigated the effect of
vitamin A deficiency on molecular
biomarkers of
iron metabolism, the inflammatory response and the erythropoietic system. Five groups of male Wistar rats were treated: control (AIN-93G), the
vitamin A-deficient (VAD) diet, the
iron-deficient (FeD) diet, the
vitamin A- and
iron-deficient (VAFeD) diet or the diet with 12 mg atRA/kg diet replacing all-trans-
retinyl palmitate by
all-trans retinoic acid (atRA).
Vitamin A deficiency reduced serum
iron and
transferrin saturation levels, increased spleen
iron concentrations, reduced hepatic Hamp and kidney
erythropoietin messenger RNA (
mRNA) levels and up-regulated hepatic and spleen
heme oxygenase-1 gene expression while reducing the liver HO-1 specific activity compared with the control. The FeD and VAFeD rats exhibited lower levels of serum
iron and
transferrin saturation, lower
iron concentrations in tissues and lower hepatic Hamp
mRNA levels compared with the control. The treatment with atRA resulted in lower serum
iron and
transferrin concentrations, an increased
iron concentration in the liver, a decreased
iron concentration in the spleen and in the gut, and decreased hepatic Hamp
mRNA levels. In summary, these findings suggest that
vitamin A deficiency leads to ineffective erythropoiesis by the down-regulation of renal
erythropoietin expression in the kidney, resulting in erythrocyte malformation and the consequent accumulation of the
heme group in the spleen.
Vitamin A deficiency indirectly modulates systemic
iron homeostasis by enhancing erythrophagocytosis of undifferentiated erythrocytes.