Page 1018 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

950 SECTION | XIV Poisonous Plants

VetBooks.ir effect on atrioventricular conduction time and QRS dura- (Fiedler and Perron, 1994), budgies (Shropshire et al.,
1992), canaries (Arai et al., 1992), and monkeys (Lacasse
tion. Even at the highest concentration used (10 μM),
et al., 2007). It is interesting to note that yew (T. baccata)
taxine A induced only mild reductions in heart rate
(Alloatti et al., 1996). is often eaten by white-tailed deer and roe deer in the
More detailed investigations of the effects of taxine United States without apparent adverse effects (Weaver
extracts on cardiomyocytes and axons indicated that taxi- and Brown, 2004; Angus, 2010). This may be due, in
nes cause an increase in cytoplasmic calcium, acting as part, to increased ruminal detoxification of the taxines
calcium and sodium channel antagonists (Smythies et al., present in the yew (Weaver and Brown, 2004).
1975; Tekol, 1985; Tekol and Kameyama, 1987; Tekol Because of the difficulties in obtaining purified,
and Go ¨gu ¨sten, 1999). In addition, isolated aorta, atrium, stable taxines in quantities sufficient for mammalian stud-
and jejunum from rabbits were used to compare the cardi- ies, in the past, minimum lethal dose (LD min ) values were
oselectivity of taxines to verapamil, a known calcium assessed through the oral administration of yew leaves and
channel antagonist. From these experiments, Tekol and branches (Watt and Breyer-Brandwijk, 1962; Clarke and
Go ¨gu ¨sten concluded that the mechanism of action of taxi- Clarke, 1988). Estimating that 1 g of yew leaves contains
nes is primarily based on calcium channel antagonistic approximately 5 mg of taxines (Smythies et al., 1975;
properties. Therefore, it is likely that the toxicity of taxi- Tekol, 1985; Jenniskens et al., 1996; Tekol and Go ¨gu ¨sten,
nes in animals and humans also occurs through the same 1999), minimal toxic doses of taxines (mg/kg body
mechanism. weight) in animals can be estimated and are summarized
Taxine alkaloids have minimal toxic effects on other in Table 66.2. The body weights of the animals listed are
organs. In the few studies reported, crude taxine extracts average values for adult animals only (Spector, 1956).
have some adverse effects on involuntary muscle, but not From Table 66.2, it is evident that the minimal toxic dose
on voluntary muscle. Uterine contractions, relaxation of of taxines varies among species. Comparatively, horses
the intestines, and contraction of the duodenum and ileum are more sensitive (LD min of 1.0 2.0 mg/kg) and chickens
have been noted in experimental animals dosed with yew are least sensitive (LD min of 82.5 mg/kg) to yew toxins.
extracts (Bryan-Brown, 1932; Vohora, 1972). Tekol and Adverse clinical signs in animals can vary depending
Go ¨gu ¨sten (1999) reported that taxine sulfate inhibited on the amount of yew ingested. However, in most cases
peristaltic movement in rabbit jejunum, with a median of acute poisoning, animals are often found dead within
25
inhibitory concentration (IC 50 ) of 1.86 3 10 g/mL. 24 h or fewer after ingestion without demonstrating
abnormal behavior or adverse signs of toxicity. In sub-
acute poisonings, which have been reported infrequently,
TOXICITY
clinical signs may include ataxia, bradycardia, dyspnea,
With the exception of the fleshy aril that surrounds the muscle tremors, recumbency, and convulsions leading to
seed, all parts of the yew plant contain taxine alkaloids collapse and death (Evers and Link, 1972; Casteel and
and are extremely poisonous. One study in laboratory Cook, 1985; Veatch et al., 1988; Evans and Cook, 1991;
rodents indicated that higher toxicity was found in the Tekol, 1991; Arai et al., 1992).
stems compared to the needles (leaves) (Shanker et al., In cases of deliberate yew poisoning in humans,
2002). Although maximal concentrations occur during the adverse symptoms of toxicity are similar to those reported
winter (Watt and Breyer-Brandwijk, 1962), toxic amounts in animals. Documented clinical signs in humans include
of taxines remain in the plants throughout the year and dizziness, mydriasis, nausea, vomiting, diffuse abdominal
are not appreciably decreased by drying (Alden et al., pain, tachycardia (initially), severe right ventricular dila-
1977). It has been reported that the cardiotoxic taxines A tation with biventricular dysfunction, muscle weakness,
and B are relatively abundant in English yew (T. baccata) and convulsions (Blyth, 1884; Czerwek and Fischer,
and Japanese yew (T. cuspidata), but only minimal 1960; Fro ¨hne and Pribilla, 1965; Schulte, 1975; Wilson
amounts are found in Pacific yew (T. brevifolia)(Tyler, et al., 2001; Panzeri et al., 2010). In some cases, these
1960; Suffness, 1995; Brown, 2003). symptoms proceed to bradycardia, bradypnea, diastolic
Clinical cases resulting in poisoning are often acciden- cardiac standstill, or death (Blyth, 1884; Fro ¨hne and
tal and are frequently a result of livestock or animals Pribilla, 1965; Schulte, 1975; Sinn and Porterfield, 1991).
being unwittingly fed clippings from yew bushes. Yew
intoxication has been reported in cattle (Casteel and DIAGNOSIS
Cook, 1985; Panter et al., 1993), horses (Tiwary et al.,
2005), sheep (Rae and Binnington, 1995) and goats Diagnosis of yew poisoning in animals is frequently based
(Coenen and Bahrs, 1994), dogs (Evans and Cook, 1991; on history of exposure. Frequently, poisoning is associ-
Taksdal, 1994), a bear (Bacciarini et al., 1999), fallow ated with pruning bushes and then feeding the trimmings
deer (Wacker, 1983), a moose (Handeland, 2008), emus to the livestock. In some cases, yew fragments (sometimes