Page 491 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

458 SECTION | V Metals and Micronutrients

VetBooks.ir protein synthesis, i.e., peptide elongation can be affected may cause damage to the kidney, and also in the stomach
Inorganic mercury, if swallowed in large quantities,
by the high concentrations of mercury, but the first stage
and intestine, including nausea, diarrhea and ulcers.
of synthesis associated with tRNA may be the most sensi-
tive. Methylmercury inhibits one or more of the amino Animal studies revealed that long-term oral exposure to
acyl tRNA synthetase enzymes. Microtubules are essential inorganic mercury salts causes kidney damage, an
for cell division (main component of the mitotic spindle), increase in blood pressure and heart rate, and effects on
and methylmercury reacts with the SH groups on tubulin the stomach. Studies also show that nervous system dam-
monomers, and thereby disrupts the assembly process. age occurs after long-term exposure to high levels of inor-
The dissociation process continues, and this leads to depo- ganic mercury. Short-term, high-level exposure of
lymerization of the tubule. Excess generation of reactive laboratory animals to inorganic mercury has been shown
oxygen species and inhibition of antioxidant enzyme to affect the developing fetus and may cause termination
appear to be the major mechanisms in methylmercury- of the pregnancy.
induced neurotoxicity (Franco et al., 2009; Farina et al., Laboratory animals exposed to long-term, high levels
2009, 2011a,b; Hwang, 2012; Kirkpatrick et al., 2015). of methylmercury or phenylmercury showed damage to
The most recent findings suggest that methylmercury trig- the kidneys, stomach and large intestine, changes in blood
gers multiple pathways, which may be activated concomi- pressure and heart rate, and adverse effects on the devel-
tantly, and ensuing cell death by apoptosis (Ceccatelli oping fetus, sperm and male reproductive organs, as well
et al., 2010; Farina et al., 2011a,b; Sokolowski et al., as increases in the number of spontaneous abortions and
2011). stillbirths.
In all forms, mercury accumulates in the kidneys, and In livestock animals, clinical signs of mercury poison-
thereby causes greater damage to this organ. The kidney ing vary greatly. In cattle, toxicity signs include ataxia,
damage appears to be dose dependent, and that means neuromuscular incoordination and renal failure, followed
recovery can occur if exposure is at low-level. Following by convulsions and a moribund state. Average time from
entry of the mercuric or methylmercuric ion into the prox- ingestion to death is reported to be about 20 days.
imal tubular epithelial cells via transport across the brush- Ingestion of phenylmercuric acetate may cause sudden
border or basolateral membrane, mercury interacts with death with massive internal hemorrhage, without other
thiol-containing compounds, such as glutathione and signs of toxicity (Puls, 1994). In horses, signs of acute tox-
metallothionein. This interaction initially produces altera- icity include severe gastroenteritis and nephritis. In
tions in membrane permeability to calcium ions and inhi- chronic cases, signs may include neurological dysfunction,
bition of mitochondrial function. Subsequently, by laminitis, in addition to renal disease, which is character-
unknown signaling mechanisms, mercury induces the syn- ized by glycosuria, proteinuria, phosphaturia, reduced
thesis of glutathione, glutathione-dependent enzymes, urine osmolarity, reduced glomerular filtration rate, azote-
metallothionein and several stress proteins. Finally, epi- mia and elevated creatinine and blood urea nitrogen. In
thelial cell damage occurs in the kidney as a result of sheep, the poisoning is characterized by severe neurologi-
excess free radical formation and lipid peroxidation, and cal symptoms and tetraplegia. Pigs show incoordination,
inhibition of antioxidant enzymes. unstable gait, lameness, recumbency and death.
Some of the toxic effects are described below in detail
for each organ/system affected by mercury exposure.
TOXICITY

In general, the toxic effects of mercury depend upon the Nervous System
form of mercury, the dose, duration and route of expo-
sure. Mercury, in all forms, has been found to be toxic to Adverse effects on the nervous system of animals occur at
both man and animals. There are many similarities in the lower doses than do harmful effects to most other systems
toxic effects of the various forms of mercury, but there of the body. This difference indicates that the nervous
are also differences. Practically, it is organic mercury, system is more sensitive to mercury than are other organs
which is more toxic and often encountered in poisonings in the body. Animal studies also provide evidence of
following oral ingestion. The major targets of toxicity to damage to the nervous system from exposure to methyl-
inorganic and organic mercury are the kidneys and the mercury during development, and findings suggest that
CNS, respectively. the effects worsen with age, even after the exposure stops.
Signs and symptoms associated with short-term expo- The reason for this greater susceptibility is that mercury
sure to metallic mercury may include nausea, vomiting, affects processes unique to the developing nervous sys-
diarrhea, increase in blood pressure or heart rate, skin tem, namely cell migration and cell division (Clarkson,
rashes, and eye irritation. 1987; Ni et al., 2017).