Page 261 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

228 SECTION | II Organ Toxicity

VetBooks.ir Additional information on plants and their effect on diterpene alkaloids act as neuromuscular blocking agents,
and the other two classes of steroidal alkaloids are sola-
the cardiovascular system is found in Beasley (1999),
num (a cholinesterase inhibitor) and veratridine (a hypo-
Knight and Walter (2001) and Hoffman et al. (1975).
Detailed treatment of plant toxicants are also available in tonic) (Schep et al., 2006). The glycoalkaloid solanine
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Cheeke (1989). opens K channels of mitochondria and increases Ca ,
while tropane alkaloids are anticholinergic and cause
arrhythmias, bradycardia, and tachycardia. Plants that har-
PHYTOCHEMICALS AFFECTING THE bor alkaloid toxins include Larkspur, Yew, Monkshood,
Ground Hemlock, and Death Camas. The Lily family con-
CARDIAC SYSTEM
tains the alkaloid veratridine, a depolarizing agent that
Plants contain on average a dozen different compounds causes persistent opening of voltage-gated Na 1 channels
that may cause cardiotoxicity, but two are of primary and reduces channel conductance by three-quarters
importance for inducing toxicity when consumed—glyco- (Table 14.1).
sides and alkaloids.
Glycosides, with a digitalis-like effect, are lethal in
GLYCOSIDE-CONTAINING PLANTS
domestic animals upon ingestion of 100 200 mg/kg of
body weight (b.w.). Asclepias spp. (Milkweed) is a perennial plant indigenous
Mechanism of toxicity of glycosides at the cellular to the Great Plains and from North Carolina to Maine
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level involves interference with the Na /K -ATPase (Kingsbury, 1964; Stevens, 2000). Most toxic is
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(Na /K -ATPase pump) resulting in decreased intracellu- Labriform Milkweed followed by the narrow-leaf
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lar K , increase in serum K 1, and consequently decreased Whorled Milkweed that exudes a milky juice from its bro-
resting potential. At high concentrations, glycosides in the ken surfaces. Galitoxin, the toxic principle, is found in all
heart affect electrical conductions, resulting in increased vegetative parts of the plant. In addition, it contains car-
vagal tone to the atrioventricular (AV) and the sinoatrial denolides that may produce digitalis-like symptoms.
(SA) nodes. This may culminate in cardiac arrhythmias Horses, cattle, and sheep are all susceptible, with a
and asystole (cardiac arrest). Additionally, they cause dosage of Whorled Milkweed of 0.1% 0.5% b.w. of the
hemorrhage, myocardial lesions, and myocarditis (Botha, animal being fatal. Cardiac signs include bradycardia or
2013). tachycardia, hypotension, and arrhythmia. Histological
More than 200 cardiac glycosides are known. Digoxin, lesions and myocarditis are common (Clark, 1979).
from Digitalis purpurea and Digitalis lanata (foxglove), Treatment includes activated charcoal lavage and a
the ingredient of digitalis, is used to enhance myocardial cathartic.
contractility but has a narrow therapeutic index. Overdose Persea americana (Avocado) of the family Lauraceae
induces ECG changes such as ST-depression, T-wave is a tree found in Mexico and commercially grown in the
inversion, PR-interval prolongation, and QT-interval United States. The toxic principle is persin that causes
decrease thereby leading to the signs of cardiac toxicity. myocardial necrosis in birds and mammals. Mastitis
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Digoxin interferes with the binding sites of K ions on the (necrosis and hemorrhage) of mammary gland epithelium
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Na /K -ATPase pump. This increases the level of Na has been observed. Sheep fed 2.5 g/kg b.w. for 32 days
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ions in the myocytes that induces higher intercellular Ca developed cardiac insufficiency. Upon ingestion of avo-
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ion presence. Excessive Ca increases cardiac contrac- cado, dogs also develop cardiac insufficiency. At high
tions. In addition, cardiac glycosides have vagotonic doses, exceeding 100 mg/kg b.w., the myocardium is
effects, resulting in bradycardia and heart block (Beasley, affected (Oelrichs et al., 1995) with necrosis of myocar-
1999; Liu et al., 2010). Treatment for glycoside poisoning dial fibers. Goats fed fresh avocado show cardiac distress
usually involves multidose activated charcoal and atropine. (Grant et al., 1991). Treatment is symptomatic and
Next to glycosides, alkaloids from plant ingredients nonspecific.
play an important role in cardiac toxicity. Alkaloids are Digitalis purpurea spp. (Foxglove) is a biennial plant
metabolites, nontoxic to the organism producing them and found in the northeastern United States as well as
toxic to foreign organisms. Their function is mainly California and states to the north. The poisonous constitu-
endogenous as regulators of metabolism to mimic neuro- ents in Foxglove include digitoxin, digitonin, and digi-
transmitters and also to influence plant growth. Alkaloids talin. The LD 50 of digitoxin for cats is 0.18 mg/kg b.w.
exhibit cytotoxicity against cells of foreign organisms. and 60 mg/kg b.w. for guinea pigs. Poultry as well as
Among others, they can be acetylcholinesterase (AChE) ruminants are affected (Thomas et al., 1987). Important
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inhibitors and Ca antagonists (Aniszewski, 2007). cardiac drugs are derived from Foxglove, including digi-
The alkaloids from roughly 20 botanical families talis that helps to increase the force of contraction of the
are significant for their cardiac effects. The polycyclic heart muscle. However, the effects of cardiac glycosides