Page 466 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

VetBooks.ir Chapter 28

Iron

Stephen B. Hooser

INTRODUCTION transport chain are essential for oxidative phosphorylation
and energy production. Iron is also contained in enzymes
Iron is an essential element for animal and plant life. It
of the Krebs cycle and in cytochromes P450, which are
works as an oxygen (O 2 ) carrier in hemoglobin/myoglobin
necessary for the metabolism of chemicals (Fairbanks,
and is involved in numerous biological oxidation reduction
1994).
reactions, including photosynthesis. Iron is present in cyto-
The iron content of feedstuffs can be highly variable
chrome P450 and is crucial for the metabolism of many che-
depending on the components. Iron in plants is subject to
micals in the liver, kidney, and other organs. Deficiencies in wide variation depending on the type of plant and the
iron can result in anemia. Excess iron can cause iron over-
amount of iron in the soil, while many animal-based feed
load and organ damage, while oxidation of ferrous to ferric
components are often rich in usable iron. The iron content
iron in hemoglobin results in methemoglobinemia and an
of water can also vary greatly (Klasing, 2005). Large
inability of red blood cells (RBCs) to carry O 2 .
amounts of iron in water give the water a rusty color and
Consequently, because of its importance, the uptake, distri-
a metallic taste, but upper limits of iron in drinking water
bution, storage, and excretion of iron is very tightly regu-
for livestock and poultry have not been established since
lated in animals under normal conditions. Because of their
experimental data are not sufficient to make definite
reactivity, free iron compounds are sequestered with proteins
recommendations (NRC, 1974).
to ensure that they do not initiate intracellular oxidative
Worldwide, iron-deficiency anemias affect large num-
damage through electron donation and the formation of reac-
bers of people, but nutritional iron deficiencies are much
tive oxygen species (ROS) such as hydroxyl radical. In this
less of a problem in animals. However, there are groups
chapter, we will deal primarily with clinical animal expo-
of animals that are vulnerable to iron deficiency including
sures to excess iron through ingestion, parenteral administra-
newborn piglets, veal calves, and those animals with para-
tion, or genetic iron storage abnormalities. Nutritional
sitic infestations (Underwood, 1977). For instance, new-
deficiencies or exposure to chemicals causing methemoglo-
born piglets have very low concentrations of liver iron
bin formation such as nitrates in ruminants, or nitrites and
(29 mg/kg) compared to newborn rabbits whose liver iron
chlorates in all species, are discussed elsewhere.
stores average 135 mg/kg.
There is accumulating experimental evidence in labo-
BACKGROUND ratory animals that excessive iron deposits in the brain
and abnormal iron homeostasis play an important role in
Iron is abundant in the universe and is the fourth most
neurodegenerative diseases such as Alzheimer’s disease
abundant element on earth. Its atomic number is 26 and
and Parkinson’s disease (Connor et al., 1995; Lan and
its atomic weight is 55.847. It has been recognized to be
Jiang, 1997; Fredriksson et al., 1999; Dal-Pizzol et al.,
an essential nutrient for more than 100 years and is pres-
2001; Qian and Shen, 2001; Arosio and Levi, 2002;
ent in all the cells of the body. The largest amount of iron
Jomova et al., 2010; Singh et al., 2013; Ward et al., 2014;
is incorporated into proteins, hemoglobin, and
Zecca et al., 2004).
myoglobin. Within RBCs (erythrocytes), hemoglobin
transports O 2 from the lungs to cells throughout the body,
while myoglobin binds O 2 for use in muscle cells PHARMACOKINETICS/TOXICOKINETICS
(Klasing, 2005). Iron present in the serum is bound to the
protein transferrin and in milk is bound to lactoferrin. The homeostatic regulation of iron in the body is complex
Iron-containing proteins in the mitochondrial electron and involves uptake, transport, utilization, storage, and
Veterinary Toxicology. DOI: http://dx.doi.org/10.1016/B978-0-12-811410-0.00028-3
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