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

Abstract

Approximately two billion people, mainly women and children, are iron deficient. Two studies examined the effects of iron deficiency and supplementation on rats. In study 1, mitochondrial functional parameters and mitochondrial DNA (mtDNA) damage were assayed in iron-deficient (<5 g͞day) and iron-normal (800 g͞day) rats and in both groups after daily high-iron supplementation (8,000 g͞day) for 34 days. This dose is equivalent to the daily dose commonly given to iron-deficient humans. Iron-deficient rats had lower liver mitochondrial respiratory control ratios and increased levels of oxidants in polymorphonuclear-leukocytes, as assayed by dichlorofluorescein (P < 0.05). Rhodamine 123 fluorescence of polymorphonuclear-leukocytes also increased (P < 0.05). Lowered respiratory control ratios were found in daily high-iron-supplemented rats regardless of the previous iron status (P < 0.05). mtDNA damage was observed in both iron-deficient rats and rats receiving daily high-iron supplementation, compared with ironnormal rats (P < 0.05). Study 2 compared iron-deficient rats given high doses of iron (8,000 g) either daily or every third day and found that rats given iron supplements every third day had less mtDNA damage on the second and third day after the last dose compared to daily high iron doses. Both inadequate and excessive iron (10 ؋ nutritional need) cause significant mitochondrial malfunction. Although excess iron has been known to cause oxidative damage, the observation of oxidant-induced damage to mitochondria from iron deficiency has been unrecognized previously. Untreated iron deficiency, as well as excessive-iron supplementation, are deleterious and emphasize the importance of maintaining optimal iron intake.

Both iron excess and iron depletion impair viability of rat H9C2 cardiomyocytes and L6G8C5 myocytes

“…This finding is consistent with the study of Walter et al [7], who demonstrated that both iron overload and iron deficiency were detrimental for the functioning of liver mitochondria [7]. It is well known that iron excess deranges the energy metabolism of tissues and constitutes a bad prognosis in patients with cardiac disorders.…”

“…Moreover, it constitutes the main component of cofactors not only for abundant globins responsible for oxygen transport and storage (haemoglobin, myoglobin), but also for numerous enzymes of the oxidative metabolism and mitochondrial functioning [2,4,6]. The particular importance of optimal iron status is well reflected by the fact that both intracellular iron excess and depletion impair the functioning of mitochondria, leading to excessive oxidative stress and deranged energy metabolism [6,7].…”

Concurrent repletion of iron and zinc reduces intestinal oxidative damage in iron- and zinc-deficient rats

“…For IRP1, which is a bifunctional protein, iron inhibits RNAbinding activity by promoting assembly of an iron-sulfur cluster in the binding protein, thereby converting it to cytosolic aconitase [42] . Walter et al [43] has suggested that iron deficiency can induce the IRP-mediated cellular iron signaling pathway, which leads to enhanced intracellular iron levels. Therefore, we assessed the activity of cytosolic and mitochondrial aconitase.…”

Iron homeostasis: An anthropocentric perspective

“…Its catalytic role depends on the ability of ferrous (Fe 2ϩ ) and ferric (Fe 3ϩ ) iron to respectively donate and accept electrons under conditions prevailing in biological systems. However, iron also promotes the formation of reactive oxygen species that can damage DNA, proteins, and lipids within cells (1,2). Multiple mechanisms have evolved to chaperone iron and to regulate its concentrations through the coordinated modulation of transport, storage, and iron utilization so that adequate iron is available for physiological functions with tolerable toxicity.…”