Both Iron Deficiency and Daily Iron Supplements Increase Lipid Peroxidation in Rats

Abstract

Numerous studies have shown that iron-loaded diets increase markers of lipid peroxidation in rats, but few have addressed the effects of oral iron supplements on these markers. We investigated the effects of daily and intermittent iron supplements on iron and vitamin E status, and lipid peroxidation. Iron supplements were administered in doses equivalent to those often given to pregnant women in the developing world. In Study 1, iron-deficient (D) and iron-normal (N) rats were fed either 0 or 8000 microgram of supplemental iron daily for 21 d. In Study 2, D rats were fed either the same supplements daily or once every 3 d (8 supplements total). Lipid peroxidation was assessed by breath ethane and pentane and by malondialdehyde (MDA) (using GC-MS). In Study 1, daily supplemented N and D rats had liver nonheme iron concentrations that were 1.8- and 2.7-fold higher, respectively, than those in unsupplemented N rats. Breath ethane levels were also higher in supplemented rats (P < 0.05), but MDA (in plasma, liver, kidney) and liver vitamin E did not differ. Unexpectedly, severely D, anemic rats had significant elevations in the levels of breath ethane, liver MDA and kidney MDA. In Study 2, liver iron and breath ethane decreased progressively (P < 0.05) from 1 d to 3 d after the last iron dose in intermittently supplemented rats. We conclude that iron deficiency results in lipid peroxidation, but that its correction with daily iron supplements results in abnormal iron accumulation and increased lipid peroxidation in rats. These effects are mitigated by intermittent iron supplementation.

Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats

“…Severely anemic, iron-deficient rats, as well as rats supplemented daily with high iron, were shown previously to have increased lipid peroxidation, as indicated by elevated levels of malondialdehyde in liver and kidney and ethane in breath (9). The current study shows that iron deficiency increased oxidant levels in PMNs and mitochondrial fluorescence of Rh123 (in PMNs and lymphocytes) and liver mtDNA damage.…”

“…We unexpectedly observed that irondeficient rats also had markedly increased lipid peroxidation (9), suggesting that both iron deficiency and iron excess promote oxidative stress.…”

“…The iron-deficient rats and those that received daily high iron had impaired liver mitochondrial RCR relative to the iron-normal rats as well as higher levels of oxidants and lipid peroxidation (9). The low RCRs indicate an uncoupling of electron transport to oxidative phosphorylation.…”

“…We have found that equivalent doses of daily high-iron supplements in rats (i.e., 10 ϫ normal intake, or 8,000 g iron͞day) results in an abnormal accumulation of intestinal mucosal (8) and hepatic nonheme iron and significant increases in lipid peroxidation (9). We unexpectedly observed that irondeficient rats also had markedly increased lipid peroxidation (9), suggesting that both iron deficiency and iron excess promote oxidative stress.…”

“…Although studies of iron deficiency previously have documented either impaired mitochondrial function (18) or increased oxidant stress (9,20), no studies have related the two phenomena. Furthermore, no studies have investigated whether iron deficiency can cause mtDNA damage.…”