Page 490 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Mercury Chapter | 31 457

VetBooks.ir follow a one-compartment or two-compartment model. more of the following effects: increased oxidative stress,
mitochondrial dysfunction, changes in heme metabolism,
Studies have shown that repeat or continuous exposure to
glutathione depletion, increased permeability of the BBB
any form of mercury can result in the accumulation of
mercury in the body. In vertebrates, mercury tends to accu- and disruption of microtubule formation, protein
mulate in the liver and kidney, but it also has a high- synthesis, DNA replication, DNA polymerase activity,
affinity for the brain and endocrine system. Mercury in the calcium homeostasis, synaptic transmission and immune
brain may persist long after cessation of short- and long- response (Farina et al., 2011a,b; Sharma et al., 2014;
term exposures. Blood levels of mercury are closely Ni et al., 2017).
related to its levels in the whole body during the first 3 The nervous system is especially sensitive to mercury.
days following administration. Thereafter, the amount of The degree of damage depends upon the form of mercury
mercury in the blood declines more rapidly than the and its dose. The effects of Hg on the developing central
whole-body burden. Animal studies show disparity in mer- nervous system (CNS) are more severe than those in the
cury body burden in terms of gender. In general, females mature CNS (Taber and Hurley, 2008; Eriksson et al.,
are believed to have higher body burdens of methylmer- 2010; Sokolowski et al., 2011; Bernhoft, 2012; Ni et al.,
cury at given doses than males. Furthermore, in rodents, 2017). Metallic mercury at high doses causes irreparable
females accumulate more mercury in the brain, while damage to the brain. In many poisoning incidents, perma-
males accumulate higher levels of mercury in the kidneys. nent damage to the brain occurred by methylmercury.
Evidence suggests that the metabolism of all forms of Since inorganic mercury does not readily cross the BBB, it
mercury is similar for humans and animals. Mercury is is highly unlikely that inorganic mercury may cause any
metabolized through the oxidation reduction cycle that damage to the brain or nerves. Most of the information
takes place in intestinal microflora, and after absorption in concerning neurotoxicity in humans following oral expo-
many tissues and in the red blood cells. Elimination rates sure to organic mercury comes from reports describing the
for methylmercury appear to vary with species, dose, sex, effects of ingesting contaminated fish or fungicide-treated
and strain. The elimination half-life in the blood of mon- grains, or meat from animals fed such grains. Studies con-
keys receiving inorganic and organic mercury was found ducted in experimental animals strongly indicate that
to be 26 days (Vahter et al., 1994). In a study of organs organic mercury is a potent neurotoxicant (Kaur et al.,
from sled dogs fed methylmercury-laden meat and organs 2007; Ceccatelli et al., 2010; Farina et al., 2011a,b; Ni
from predatory marine animals, the highest concentration et al., 2017).
of total mercury was found in the mesenterial lymph Evidence suggests that a single dose of mercuric chlo-
nodes, followed by liver and kidneys, indicating that the ride (0.74 mg/kg) caused disruption of the BBB barrier in
lymphatic system may play an important role in the trans- rats (Chang and Hartman, 1972). These investigators also
port of mercury to target organs (Hansen and Danscher, administered mercuric chloride to rats at the same dose
1995). The tissue concentrations of mercury observed in daily for 11 weeks. Within 2 weeks, there were coagula-
this study were found to be age related, and the results sug- tive or lucid changes in cerebellar granule cells and frag-
gest that demethylation takes place in all organs, except mentation, vacuolation and cytoplasmic lesions in the
the skeletal muscles. Demethylation of methylmercury neurons of dorsal root ganglia. Neurological disturbances
was found to be lower in the brain than in other organs. consisted of severe ataxia and sensory loss.
For further details on toxicokinetics of mercury refer to Neurotoxic effects seen in the Minamata (Japan) and
Bernhoft (2012). Iraqi poisonings were associated with neuronal degenera-
tion and glial proliferation in the cortical and cerebellar
gray matter and basal ganglia (Al-Saleem, 1976).
MECHANISM OF ACTION
Derangement of basic developmental processes, such as
Toxicities of the different forms of mercury are related, in neuronal migration (Matsumoto et al., 1965; Choi et al.,
part, to its differential accumulation in sensitive tissues. 1978) and neuronal cell division (Sager et al., 1983) were
This theory is supported by the observation that mercury also observed. In the brain, Purkinje, basket, stellate and
rapidly accumulates in the kidneys and specific areas of granule cells are severely affected by methylmercury.
the brain (Yilmaz et al., 2014; Pletz et al., 2016; Ni et al., Methylmercury selectively inhibits protein synthesis in
2017). High-affinity binding of the divalent cationic mer- the brain (reversibly in neurons from the cerebrum and
cury to thiol or sulfhydryl groups of proteins is believed Purkinje cells; and irreversibly in granule cells of the cer-
to be a major mechanism involved in the toxicity of mer- ebellum), and this effect usually precedes the appearance
cury. As a result, mercury can cause inactivation of vari- of clinical signs. This selective action on the brain may
ous enzymes, structural proteins, transport proteins and be due to the fact that certain cells are susceptible because
alteration of cell membrane permeability by the formation they cannot repair damage from methylmercury. Cheung
of mercaptides. In addition, mercury may induce one or and Verity (1985) identified the most sensitive step in the