Multiple mechanisms account for lower plasma iron in young copper deficient rats

Abstract

Copper deficiency lowers brain copper and iron during development. The reduced iron content could be due to hypoferremia. Experiments were conducted to evaluate plasma iron and "ferroxidase" hypotheses by determining copper and iron status of Holtzman albino rats following gestational/ lactational copper deficiency. Copper deficient (Cu−) dams on treatment for 5 weeks, two of gestation and three of lactation, had markedly lower copper content of milk and mammary tissue, and lower milk iron. Newborn pups from Cu− dams had lower copper and iron concentrations. Compared to Cu+ pups, Cu− pups, analyzed between postnatal age (P) 0 and P26, were smaller, anemic, had lower plasma iron, cardiac hypertrophy, and near zero ceruloplasmin activity. Liver copper in Cu+ pups increased then decreased during development and major reductions were evident in Cu− pups. Liver iron in Cu+ pups decreased with age while nursing but increased after eating solid food. Liver iron was lower in Cu− pups at P0 and P13 and normal at P20 and P26. Small intestinal copper decreased with age in Cu+ pups and was lower in Cu− pups. Intestinal iron levels in Cu-pups were higher than Cu+ pups postweaning in some experiments. Reduction in plasma iron in Cu− pups is likely due to a decreased "ferroxidase" function leading to lower placental iron transport, a lower milk iron diet, and partial block in iron uptake from intestine but is not due to failure to mobilize hepatic iron, in contrast to older rats eating diet with adequate iron.

Copper deficiency has minimal impact on ferroportin expression or function

“…This was demonstrated by detection of low neonatal liver iron and copper in CuD rat pups (Andersen et al 2007;Pyatskowit and Prohaska 2008b). Similar studies showed that iron content of newborn CuD mouse pups was lower than CuA pups (Pyatskowit and Prohaska 2008c). Perinatal CuD rat pups also have lower brain iron (Fig.…”

“…Thus, for intestine of CuD rats and mice there should be iron retention if hephaestin function is compromised. Previous work summarizing six experiments from our lab suggested that small intestinal Fe was rarely augmented with the exception of the upper duodenum (Pyatskowit and Prohaska 2008c). Others have reported higher iron levels in intestine of CuD rats .…”

“…After weaning when dietary iron content rises sharply as pups switch from milk to solid food (50 mg Fe/kg), intestinal iron has Values are means ± SEM. Cu-deficient means were significantly different than Cu-adequate, *P \ 0.05 (Student's t-test) been reported to become augmented in CuD rat pups compared to CuA controls (Pyatskowit and Prohaska 2008c). Limited studies on CuD mice suggest they retain iron in intestine after lactational Cu deficiency (Chen et al 2006).…”

“…Others have reported higher iron levels in intestine of CuD rats . At birth CuD pups are irondeficient (FeD) based on fetal Fe content of liver or whole rat pup iron content (Andersen et al 2007;Pyatskowit and Prohaska 2008c). After weaning when dietary iron content rises sharply as pups switch from milk to solid food (50 mg Fe/kg), intestinal iron has Values are means ± SEM.…”

Perinatal Iron and Copper Deficiencies Alter Neonatal Rat Circulating and Brain Thyroid Hormone Concentrations

“…Brain Fe content was corrected for blood contamination (23). Serum Fe concentrations were determined by flame AAS after hemoglobin was removed (25).…”