Toxic Plants: What the Horse Practitioner Needs to Know

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TOXICOLOGY

TOXIC PLANTS What the Horse Practitioner Needs to Know A. Catherine Barr, PhD, and John C. Reagor, PhD

Horses are generally selective about what they eat while on pasture, and for the most part, this makes them less likely than other livestock to be poisoned by toxic plants. Situations in which poisoning becomes more likely should be avoided. As with other livestock, horses introduced to a new area are more likely than native animals to be poisoned by plants. Horses are frequently confined to small spaces and left unattended for long periods of time; as a result, they are prone to sample any greenery available out of boredom. Access to areas treated with herbicides should be avoided until all the treated plant material is dead, because treatment may change palatability or increase toxicity in some plants. Horses are at the mercy of toxic plants when these plants are present in hay and feeds. The only solution is for owners to know their suppliers and to watch for recognizable contamination. Most plant poisonings have no specific treatments. Survival usually depends on decontamination, with supportive and symptomatic care. GASTROINTESTINAL

There are many grasses and forbs that produce seed coats, awns, or thorns capable of wounding the oral mucosa, allowing formation of abscesses. Foxtail and bristlegrasses (Setaria spp) as well as sandbur (Cenchros pancufloris spp) are notorious hay adulterants. 7 Frequently,

From the Texas Veterinary Medical Diagnostic Laboratory and Department of Veterinary Anatomy and Public Health, Texas A & M University, College Station, Texas

VETERINARY CLINICS OF NORTH AMERICA: EQUINE PRACTICE VOLUME 17 • NUMBER 3 • DECEMBER 2001

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horses refuse to eat hay containing these sharp-barbed seeds. Horses have also been known to ingest some species of cacti when forage is lacking and they are forced to consume short grass in and around the cacti. In general, most plants with an odor, be it aromatic or fetid, contain essential oils, and many of these can irritate the gastrointestinal mucosa of the horse. Some are much more irritating than others, and individual animal sensitivity also plays a role in the reactions of the animals. Odiferous plants cause some degree of diarrhea, and some animals may react with colic. Plants of the buttercup family (Ranunculaceae) are found growing in wet soils and marshy areas throughout North America. They contain varying concentrations of ranunculin. When the plant is crushed, ranunculin is converted to protoanemonin, a strong irritant that can blister the lips and irritate the oral and digestive mucosae. Clinical signs to be expected include salivation, abdominal pain, and diarrhea. Fresh buttercups are not palatable to horses, and the dried plant material is no longer toxic; thus, the hazard is slight. 6• 7 Seeds from corn cockle (Agrostemma githago) contain a saponin that irritates the gastrointestinal tract, resulting in anorexia, diarrhea, and a rough hair coat when the seeds are present in horses' feed. 7 Nightshades (Solanum spp) are found all over North America, and their toxicity varies considerably with species, soil type, climate, and season. Some species are not consumed by horses unless they are baled into hay (e.g., buffalo bur [S. rostratum]). Buffalo bur has broad prickly leaves and five-lobed yellow flowers followed by fruits enclosed in spiny capsules. Less forbidding species more frequently eaten and implicated in pasture poisonings include black nightshade (S. ptycanthum), bittersweet (S. dulcamara), silverleaf nightshade (S. elaeagnifolium), Carolina horse nettle (S. carolinense), and western horse nettle (S. dimidiatum). All these plants bear the typical white or purple five-lobed blooms followed by tomato-like fruits of varying size, which are purple-black (black nightshade), orange (bittersweet), or yellow. 2 The nightshade toxins include alkaloids, a mixture of heat-stable steroidal glycoalkaloids, and cholinesterase inhibitors. The primary toxicant, solanine, is a steroidal alkaloid that acts as a local irritant and is poorly absorbed from the gastrointestinal tract. As a consequence, it causes anorexia, salivation, abdominal pain, and diarrhea; the absorbed toxin causes dilation of the pupils, dullness, depression, weakness, progressive paralysis, and prostration, and it can be fatal. 13 Consumption of 0.1% to 0.3% of the animal's body weight in ripe silverleaf nightshade berries can cause moderate to severe poisoning. 1 There is also an apparent potentiation of poisoning when horses eating silverleaf nightshade are treated with ivermectin. 4 Castor bean (Ricinus communis) has been raised across the southern United States as an oilseed, and it is also grown as an ornamental plant because of its blue-green dinner plate-sized leaves and 10- to 12-ft height. By far the most toxic part of the plant is the seed, which contains

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ricin, a lectin or toxalbumin that acts by disrupting protein synthesis at the ribosomal (subcellular) level. The toxin is also antigenic; if it is ingested by a sensitized animal, anaphylaxis may result. After consumption of a toxic dose of seeds, usually in contaminated feed, there is a latent period lasting several hours to 2 days before the horse becomes dull and depressed with abdominal pain and nonhemorrhagic watery diarrhea, slight incoordination, fever, and profuse sweating, possibly with spasms in the neck and shoulder muscles. Respiration and heart rates increase, and cardiac contractions may be strong enough to be seen from several feet away. The animal usually dies 24 to 36 hours after ingestion of a lethal dose, estimated at 50 g of seeds. 6 · 8 • 13 Other plants whose poisoning syndromes include significant gastrointestinal signs include oleander (Nerium oleander), foxglove (Digitalis spp), and oak (Quercus spp) . HEPATIC Pyrrolizidine Alkaloid Poisoning

Pyrrolizidine alkaloids (PAs) are present in many different groups of plants and cause delayed progressive liver damage. Hepatic p450 enzymes metabolize PAs to pyrroles that cross-link double-stranded DNA and bind to proteins and nucleic acids within the hepatocytes, making it impossible for them to divide normally (antimitotic effect). There is a latency of at least 3 weeks while the initially affected hepatocytes grow without dividing to become megalocytes. As these cells die, they are replaced by fibrosis, leaving a decreasing amount of functional liver tissue. The process is irreversible, and when the animal eventually dies of PA poisoning (after 6 weeks to 2 years), the pathognomonic liver lesion includes megalocytosis and bridging fibrosis between portal triads. Biliary hyperplasia also occurs frequently. If the dose ingested is larger and the progression is more rapid, there may be a large degree of necrosis and hemorrhage. Clinically, horses early in the progression of the disease present as "poor doers." With greater exposure, the animals progress through rough hair coats, depression, and anorexia to icterus, ascites, emaciation, diarrhea or constipation, hepatoencephalopathy (head pressing, occasionally mania), and eventually death. Clinical chemistry panels tested early in the course of the illness typically show elevations in sorbitol dehydrogenase, aspartate aminotransferase (AST), and gamma-glutamyl transferase); later, total bilirubin increases and albumin decreases, as does the albumin:globulin ratio. At necropsy, the liver in the typical chronic case is firm and fibrotic. The toxic dose of PA-containing plant material is highly variable depending on the plant and part of the plant consumed. After the onset of clinical signs, the prognosis is poor. 1• 6 • 7• t 3 Some of the plants that contain PAs cause problems mostly from the standpoint of contamination of grain with their seeds. Among these

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are tarweed or fiddleneck (Amsinckia spp) growing in disturbed areas and grain fields of California and the Pacific Northwest and rattlebox (Crotalaria spp), a legume more prevalent in the southeastern United States, Hawaii, and the Missouri and Mississippi river bottoms.1• &-8, 13 Grain contamination is not always the source, however, and one group of horses pastured temporarily in a field of crotalaria (C. spectabilis) consumed a large amount of fresh plant material within a few days. Eight members of the group were found dead one morning with massive hepatic necrosis caused by the high dose of PAs (personal communication, Steve Nicholson, DVM, Baton Rouge, LA, 1999). Hound's tongue (Cynoglossum officinale) is another PA-containing plant that grows in western North America. In Colorado, 0.6% to 2.1 % of the plant on a dry matter basis (dm) in hay poisoned horses. The toxic dose was estimated to be one plant per day for 2 weeks. 1 Many of the groundsels and ragworts (Senecio spp) are known to contain PAs, and one or more species is present in most parts of North America. Tansy ragwort (S. jacobea) covers the mountain states and extends westward to the Pacific, and its flower contains four times as much PA as the leaves, which contain far more than the stems. 1 Threadleaf groundsel (S. douglasii var. longilobus) and broom groundsel (S. riddellii) cover northern Mexico and extend northward and westward into Texas, Oklahoma, Nebraska, New Mexico, and Arizona. Butterweed (S. glabellus) is prevalent over the southeastern United States as far north as Illinois. 2 Winter rosettes of these plants are some of the earliest things to become green, and they are often eaten at this growth stage when little other forage is available. By the time the plants become upright and mature w ith their typical all-yellow daisy-like blooms, animals may be showing signs derived from material they ate weeks or months before. Groundsel and fiddleneck poisoning also occurs frequently from contamination of hay and other dried forages . Hepatotoxicity and Necrosis

Various species of cocklebur (Xanthium spp, most frequently X. strumarium) grow all over North America along streams, around shallow farm ponds, and in fields. The seeds and seedlings up to the two- to fourleaf stage (cotyledonary) contain the compound carboxyatractyloside, a plant growth inhibitor that allows one seed in each two-celled capsule to germinate the first year and delays germination of the second seed until the next year. Carboxyatractyloside uncouples oxidative phosphorylation in mammalian species, causing acute hepatic centrilobular necrosis and hepatoencephalopathy with depression, weakness, prostration, opisthotonus, paddling, convulsions, coma, and death. An outstanding clinical finding is a profound hypoglycemia. Whereas a normal serum glucose level is about 100 mg/ dL, a poisoned animal has 16 mg / dL of glucose in the serum. There is also increased vascular permeability. Horses more often consume cocklebur seeds as feed contaminants than

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they do the seedlings in the field. The minimum lethal dose of cocklebur seeds is 0.3% of the horse's body weight. 1• 6 Kleingrass (Panicum coloratum) has been planted as pasture grass in the Southwest, and switchgrass (P. virgatum) is a native grass across much of North America. Both contain saponins that can cause liver damage in horses, but the saponin levels in the grasses fluctuate in response to factors not yet well understood. Clinical chemistry analysis of serum from a horse with kleingrass poisoning shows elevations in AST, lactate dehydrogenase (LOH), alkaline phosphatase (AP), and total bilirubin. 7, 13 Some ranchers in Texas have had horses on mixed kleingrass pastures for years with no clinical illness. These grasses are not palatable to horses and are only consumed when no other forage is available. Toxicity is highest during rapid growth but does not decrease with drying. Most poisoning occurs when horses are fed kleingrass hay. Horses should never be placed on monoculture kleingrass pastures. Another bovine forage crop that can cause liver damage in horses is alsike clover (Trifolium hybridum), which is grown across the northern United States and Canada. It is not particularly palatable to horses, and poisoning usually occurs after at least a year of exposure unless the pasture is overgrazed. Poisoning can occur in horses after a few weeks if alsike clover is the major forage available. Clinical signs include anorexia, loss of body condition, jaundice, hepatoencephalopathy, and death. The conditions of intoxication are not well understood, and toxicity may be a result of endophytic bacteria. 1 Occasionally, horses with alsike clover poisoning also show signs of photosensitization as a result of the combination of liver damage, which allows the accumulation of phylloerythrin (a major breakdown product of chlorophyll), and exposure to sunlight (secondary or hepatogenous photosensitization). These animals tend to avoid the sun, and they experience edema, necrosis, and sloughing of unpigmented or lightly haired areas of skin. Animals with secondary photosensitization should be housed out of the sun and given dry hay to minimize their chlorophyll intake until the liver has time to recover (usually several days after removal of the offending plant from the diet). 1• 7• 13 Lantana (Lantana camara) is an escaped ornamental bush that tends to grow in fence rows where birds have spread its seeds, mostly across southern North America. The foliage is pungent and prickly, and the dark heart-shaped leaves have serrated edges. Ornamental varieties have clusters of single-colored (dwarf: yellow, cream, lavender, red) or multicolored (bush: pink to yellow to cream) florets, and the escaped hardier variety has multicolored (red to orange to yellow) flowers. The plants with the darker flowers tend to be more toxic, and the toxicity of the recently hybridized dwarf varieties remains to be determined. The toxins in lantana are saponins called lantanadenes A and B. In addition to liver damage like that caused by the saponins in kleingrass, these compounds also cause bile duct proliferation, cholestasis, and icterus. The clinical chemistry profile typically shows markedly elevated AST, LOH, AP, gamma-glutamyl transferase, and total bilirubin. At necropsy

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of an animal that dies of lantana poisoning, the liver is typically a golden-orange color and friable. Horses poisoned with lantana sometimes show signs of secondary photosensitization. 1• 7

INTEGUMENT AND EPITHELIOIO TISSUES Primary Photodynamic Agents

The condition of primary photosensitization occurs when a sensitizing compound is consumed or comes in contact with the skin and responds to sunlight by causing cellular damage. The liver plays no role in primary photosensitization (see section on hepatotoxicity). Furocoumarins (psoralens) are the photoactive compounds in Bishop's weed (Ammi majus), which grows native in the coastal southern United States, as well as in parsley (Cymopteru s watsonii), which grows in Utah and Nevada. Bishop's weed and parsley are both umbillifers and carry blooms similar to Queen Anne's lace. 1• 6• 7• n Bishop's weed has recently been included in some wildflower seed mixes for distribution along highways and may become more widespread. Dutchman's breeches (Thamnosma texana, T. montana) contains at least nine furocoumarins and grows throughout most of the western United States. 1· 6 • 7 St. John's wort (Hypericum perforatum) is native to the Atlantic and Pacific coasts and is found throughout the southeastern United States. The plant grows 1 to 3 ft tall with yellow daisy-like flowers . Its distinguishing feature is the leaves, which seem to have numerous pinpricks-the translucent granules that contain the photoactive compound hypericin. Poisoning is rare, because a large amount of plant material is required. When poisoning occurs, clinical signs appear within 4 to 5 days of ingestion. Fagopyrin, the toxin in buckwheat (Fagopyrum saggitatwn), is a chemically elaborated version of hypericin with similar effects_ 1, 6- s, i 3 The toxin present in giant rainlily (Cooperia pedunculata) has not been identified. The small white lily is present in a band along the western Gulf of Mexico/ but it causes primary photosensitization only in a few counties in Texas. The toxicity has been localized to the decaying leaf tips and may be caused by the fungal byproducts. 12 Clinical signs for primary photosensitization include erythema and edema of white, lightly pigmented, or lightly haired areas, which later become blistered and can slough, allowing for secondary infection. 1· &-s. 13 The eyes may be affected by swelling, keratitis, or conjunctivitis. With St. John's wort and buckwheat, there may also be some intravascular hemolysis as a result of free radical damage to red blood cell membranes.1 Animals with primary photosensitization should be kept in the shade, and standard wound care should be provided.

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Granulomatous Disease

Chronic granulomatous disease results when some horses graze various species of vetch, including hairy vetch (Vicia villosa) and leavenworth vetch (V leavenworthii). Hairy vetch, introduced from Europe, grows widely across North America, although leavenworth vetch is restricted to Missouri, Oklahoma, Arkansas, and Texas. 2 Vetch, a cool season annual, becomes green early in the spring; animals usually show clinical signs associated with granulomatous disease between late spring and midsummer. The toxic agent has not been identified, and the disease seems to affect black animals primarily (same pattern in cattle). Clinical signs include weight loss in spite of good appetite, fluctuating body temperature, and subcutaneous edema. Clinical chemistry results can vary considerably depending on which organs have been affected. Death occurs as a result of multifocal or widespread granulomatous inflammation of organ systems. Effects of this disease can be seen in any combination of organs, including the skin, lymph nodes, lungs, kidneys, liver, heart, gastrointestinal tract, skeletal muscles, and eyes. 13 The course of the disease is irreversible, with the solution being not to let horses graze vetch. BLOOD DYSCRASIAS lntravascular Hemolysis

The wilted leaves of maple trees (A cer spp), found throughout North America but more prevalent in the eastern part of the country, are toxic specifically to horses. For a 1000-lb horse, 1.5 lb of wilted leaves produces toxicity, and 3 lb is lethal. Fresh leaf material is not toxic. Poisonings usually occur in the fall or after storms or trimming. The unidentified toxin causes oxidative damage to erythrocyte membranes. Early clinical signs develop at least 1 day after consumption and include anorexia, depression, weakness, and obvious methemoglobinemia; by the next day, there is intravascular and extravascular hemolysis, icterus, anemia, respiratory distress, Heinz body formation, and dark urine as a result of hemoglobinuria. By the fourth or fifth day, severely affected horses are comatose. At necropsy, there is diffuse marked icterus, splenomegaly, and swollen dark kidneys; the liver may be swollen and brownish, and any urine present may be wine-colored. If the animal did not die from anoxia and respiratory distress, it may have died from renal failure. There is a poor prognosis for red maple-poisoned horses. Response to methylene blue for the methemoglobinemia is usually limited, but ascorbic acid is somewhat more effective. Oxygen therapy may relieve the respiratory distress, but renal function must also be maintained. 1, 7 , 13 Onion (Allium spp) poisoning in horses is rare, but it also causes acute hemolytic anemia with hemoglobinuria and icterus. It occurs only when large amounts of cull onions from onion farms are fed or when

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more suitable forage is short and horses are forced to eat wild onions. The toxic principles in onions are related to N-propyl disulfide, which causes intravascular hemolysis. Differentiation of onion poisoning from maple intoxication is based on the absence of extravascular hemolysis and the much smaller degree of methemoglobinemia caused by onions. Animals generally die of hemolytic anemia and secondary renal failure caused by hemoglobinuric nephrosis. At necropsy, there is an onion odor to the carcass. 1· 13 Oxalate-induced Hypocalcemia

Soluble oxalates in some plants can cause a precipitous drop in serum calcium and sudden death. None of these plants are palatable to horses, and poisoning is rare. Many accumulate oxalates over the course of their growing season, being most toxic in fall and winter. Black greasewood (Sarcobatus vermiculatus), a western range plant, contains 10% to 20% dm soluble oxalates1 (sodium or potassium salts) at highest levels in the leaves, followed by the seeds, with the least in the stems. Clinical signs usually begin with depression, some degree of colic, weakness, and irregular gait within 2 to 6 hours of ingestion. Horses may die by 10 to 12 hours, after progressing through lateral recumbency, coma, and possible convulsions. In animals that survive this stage of poisoning, which is caused by hypocalcemia, the circulating oxalate combines with serum calcium to form insoluble calcium oxalate crystals that eventually cause renal failure by lodging in the renal tubules. A toxic but nonfatal dosage of sodium oxalate for an adult horse is 200 g/ d for 8 days.13 Clinical chemistry assays in the first phase of poisoning reveal a strong hypocalcemia, and those determined in the second phase have elevated blood urea nitrogen and creatinine. Treatment is usually of little value once clinical signs have appeared, although intravenous calcium gluconate can temporarily relieve hypocalcemia, and diuresis may help to prevent buildup of calcium oxalates in the kidneys. 1• 8 • 13 Halogeton (Halogeton glomeratus) also grows in the western rangelands, including Nevada, Utah, and Idaho, and causes only the hypocalcemic phase of toxicity,13 Curly dock (Rumex crispus) and other dock species are common noxious weeds that grow on gravelly soils and may also cause renal toxicity secondary to oxalate nephrosis.6 Hypercalcemia

Day-blooming jasmine (Cestrum diurnum), also called wild jasmine or day cestrum, grows on disturbed soils in Florida, Texas, California, Mexico, and Hawaii and is spread by birds that ingest its seeds. The plant is green and available all year, and in these areas, it can be consumed for weeks to months. It contains the steroidal glycoside 1,25-

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(OHh cholecalciferol, which disrupts normal feedback regulation and allows intestinal absorption of excess calcium, with sustained secretion of calcitonin and decreased parathyroid activity. Clinically, the animal loses weight over 2 to 6 months despite a normal appetite and exhibits increasing lameness with a humped-up appearance and a choppy gait. Clinical chemistry assays reveal a moderate to severe hypercalcemia with normal phosphorus levels. Affected horses lie down frequently, and the tendons and suspensory ligaments may be tender on palpation of the overextended fetlock joint. Consumption of the plant causes dystrophic calcification of elastic tissues, including tendons, ligaments, major arteries, and the heart; signs resolve over time after consumption of the plant ceases. 1• 8, 13 RENAL

Oak (Quercus spp) poisoning is rare in horses but does occur when high-tannin parts of the plant-the catkins (flowers), leaf buds, or acorns-are consumed in quantity. There is usually depression, an acute onset of abdominal pain, and straining and hemorrhagic diarrhea, often accompanied by hematuria, tachycardia, and tachypnea. Tannie and gallic acids are toxic to renal tubular epithelium, and the major clinical signs include dehydration, azotemia, hyperphosphatemia, hypocalcemia, and hypoproteinemia. It is important to diurese the poisoned animal and to maintain electrolyte and acid-base balances.7· 8• 13 As mentioned previously, black greasewood (S. vermiculatus), native to the western rangelands of the United States, contains soluble oxalates; these soluble oxalates combine with serum calcium to form insoluble calcium oxalate, which is then deposited in the renal tubules and can cause kidney failure. Other oxalate-containing plants covering most of North America include carelessweed or pigweed (Amaranthus spp), lamb's ear or goosefoot (Chenopodium spp), dock (Rumex spp), and kochia or Mexican fireweed (Kochia spp). Levels of oxalates in these plants are relatively low, and large amounts of plant material must be consumed before poisoning occurs.6• 13 CARDIAC AND CIRCULATORY Arrhythmias

Oleander (Nerium oleander) grows in deep bands along the southeastern and southwestern coasts of North America. The bold dark green foliage makes a striking hedge or tree and provides a sharp contrast to its bright blooms. It is resistant to insect damage; in fact, little eats it and lives. Luckily, fresh oleander is unpalatable to horses; however, its clippings are palatable. Oleander contains at least five cardiac glycosides throughout the plant, with the best characterized being oleandrin. These

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compounds alter cardiac conduction rates by their inhibition of the Na +K + adenosine triphosphatase. Sudden death w ith no gross lesions is frequent. At lower doses, clinical signs include hyperkalemia; depression; anorexia; and profuse, catarrhal, watery, or bloody diarrhea within a few hours of ingestion, followed by alternating bradycardia and tachycardia and other arrhythmias. There is also profuse sweating, peripheral vessel constriction causing cold extremities and pale mucous membranes, and muscle twitching as a result of anoxia. Weakness, coma, and death follow, often within 12 hours of ingestion of the plant material. When the course of poisoning has been slow enough, patchy cardiac necrosis and gastrointestinal hemorrhage may develop. Consumption of about 0.25 lb of plant material (about 0.005% of body weight) is fatal in less than 12 hours. 1• 6 • 13 Foxglove (Digitalis spp) contains a number of cardiac glycosides (hydrolyzed to gitoxin, digitoxin) that strengthen the force of contractions and prolong the diastolic phase. Various species of foxglove grow throughout North America and have been marketed as bedding plants in the last few years. Poisonings are rare, because horses normally do not eat the plant. Clinical signs include lethargy, gastrointestinal irritation, arrhythmias and irregular pulse rate, tremors, and convulsions. According to Kingsbury,6 a lethal dose of fresh foxglove leaf is on the order of 0.05% of body weight. 7 Most milkweeds (Asclepias spp) contain cardioactive glycosides or cardenolides in their white milky sap as well as other compounds. The bitterness of this sap also makes them unpalatable, and horses do not eat them unless they are in hay. Clinical signs include profound depression, salivation, dilated pupils, a weak rapid pulse, d yspnea, loss of muscular control, collapse, muscle spasms due to anoxia, convulsions, and death. Some animals have recovered with supportive care. The toxicity of the various species of broad- and narrow-leaved milkweeds varies considerably, and a lethal dose is estimated at 0.05% of body weight dm or 2% in green plant material. 1· 6 • 7 Members of the heath family (Ericaceae), including rhododendrons and azaleas (Rhododendron spp), laurels (Kalmia spp, Leucothoe spp), andromeda and pieris (Pieris spp), and wild rosemary (Ledum spp), are brightly flowered bushes to tall hedges growing in acid soils across much of eastern North America and up the West Coast. All aerial parts of these plants as well as the honey made from their nectar contain grayanotoxins. Poisoning occurs when these compounds bind to sodium channels in excitable cell membranes (muscle and nervous tissues), extending the time to repolarization and disrupting ion balances. Cardiac signs of grayanotoxin poisoning include bradycardia, hypotension, sweating, weakness, and arrhythmias. The neurologic effects include respiratory depression, some degree of paralysis, and possible convulsions.14 To avoid potentiation of the effects of cardiac glycosides on the myocardium, fluids containing calcium (Ca ++) should not be used to treat cardiac glycoside toxicosis. 13

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Horses that eat yew or ground hemlock (Taxus spp) are usually just found dead, sometimes with plant material still in the mouth. These small shrub-like evergreen trees grow across the northern United States and Canada, usually as dense hedges. The fresh plant material is not palatable, but the trimmings are more so, and drying does not decrease their toxicity. All parts of the plant contain taxine alkaloids, which depress cardiac conduction. Rarely, animals with yew poisoning are found lethargic, trembling, ataxic, recumbent, dyspneic, and bradycardic, sometimes with jugular pulsation and distension, and they die soon thereafter. Death may be so rapid that there are no gross lesions, or there may be myocardial hemorrhage and pulmonary congestion and edema. A lethal dose of yew is 0.1% to 0.5% of body weight. 1• 7

Myocardial Necrosis

White snakeroot or richweed (Eupatorium rugosum) grows throughout the eastern half of North America in well-drained soils of wooded pastures. The plants grow in 3- to 4-ft tall bunches and carry clusters of white composite flowers in early autumn. The toxin tremetone is freezestable and has a long half-life in the body, allowing a cumulative effect. Onset of clinical signs varies from 2 days to 3 weeks after beginning consumption and can be precipitated by any type of stress; death usually occurs 1 to 3 days after clinical signs appear. The basis is enzymatic damage to the heart (primarily) and skeletal muscles; thus, clinical signs include depression, sluggishness, stiff gait, ataxia, frequent crossings of the rear limbs, a wide-based stance, partial throat paralysis, severe sweating, labored, shallow respirations, normal to below-normal body temperature, and cardiac arrhythmias or sudden death without previous signs. Clinical chemistry assays reveal markedly increased creatine kinase, AST, and LOH, and urinalysis may indicate some degree of myoglobinuria. Histopathologic lesions include extensive patchy myocardial necrosis, moderate to severe hepatic centrilobular vacuolation, and some degree of myoglobinuric nephrosis. Tremetone is the classic example of a milk-transferred toxin; it is secreted into the milk by the dam and is consumed by the foal, whose lighter body weight increases its sensitivity to the dose it receives. Foals may show signs, although dams seem unaffected. White snakeroot is still active dried in hay, and 0.5% to 2% dm or 1% to 10% on a green plant material basis of body weight is lethal to a horse. 6 • 7• 13 Rayless goldenrod, jimmy weed, or burrow weed (Isocoma wrightii) growing in the Southwest also contains tremetone as its active compound. In rayless goldenrod and white snakeroot poisoning, myocardial damage is the most significant lesion; the secondary lesion of renal tubular nephrosis usually is pronounced more with rayless goldenrod. Consumption of 1% to 1.5°/4, body weight in plant material over 1 to 3 weeks is lethal. 0 · 7 · 13

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Hypostatic Effects

Death camas (Zigadenus spp) is a genus of a toxic lily-like plant species growing in sandy soils west of the Mississippi River as far north as Alaska and across the southeastern United States. Most poisonings occur in early spring, because death camas is one of the earliest plants available. The toxin zygacine is a steroidal alkaloid with marked hypotensive effects, causing dilation of arterioles and constriction of venous vascular beds as well as slowing of heart rate. Clinical signs begin several hours after ingestion, but death may not occur for several days. The animal experiences depression, staggering, profuse salivation, pupillary constriction, decreased respiration and heart rates, weakness, dyspnea, prostration, and death. 1· 2· 6• 8 Laminitis and Peripheral Edema

Laminitis (founder) can occur when horses are bedded on shavings consisting of more than about 20% black walnut (Juglans nigra). Clinical signs appearing 10 to 24 hours after exposure include reluctance to move, depression, shifting weight from limb to limb, increased digital pulse and temperature, and mild to pronounced limb edema. Animals removed from the bedding and cared for usually have a good prognosis. Beddings with shavings from other Juglans spp (butternut [J. cinerea], English walnut [J. regia]) should be avoided as well, as these have not been proven safe.7· 8· 13 Within 2 to 3 days of eating hay contaminated with hoary alyssum (Berteroa incana), horses stock up, that is, they suffer limb edema, with transient fever and diarrhea. They generally recover 2 to 4 days after removal of the source from their diet. 7 Gordon bladderpod (Lesquerella gordonii), another member of the mustard family, seems to cause the same syndrome, but this has not yet been confirmed by feeding trials. Hoary alyssum is found in the northern Midwest, and Gordon bladderpod grows in the Southwest. CENTRAL NERVOUS SYSTEM Thiaminase

Bracken fern (Pteridium aquilinum) grows abundantly in openly forested areas and disturbed sandy soils across the northern tier of the United States and Canada, extending southward. It is usually not consumed, except in late summer w hen other forage is scarce or when it is gathered into bedding or hay. The entire plant is toxic, containing a thiaminase whose concentration peaks in late summer and is not destroyed by drying. Horses begin to lose weight several days after the first exposure, but about 30 days of consumption pass before incoordina-

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tion is noted. Animals become progressively more ataxic, with the front legs occasionally crossing in motion, and they adopt a wide-based stance, sometimes with the back arched. Slight muscle fasciculations progress to tremors and clonic spasms, opisthotonus, and death within 2 to 10 days of the onset of signs. The prognosis is good if the basis for the illness is recognized before recumbency, although seizures may occur for 2 to 3 weeks after the animals are no longer exposed to the toxin. Hay containing as much as 20°/4, dm bracken fern is hazardous. 1· 6• 13 Horsetail, mare's tail, or scouring rush (Equisetum arvense) has a similar geographic range as bracken but tends to grow in wetter and somewhat colder areas. It also contains a thiaminase but is so unpalatable that it is only eaten when baled into hay. 1• 6 • 13 Treatment is based on replacing thiamine in the system. Nigropallidal Encephalomalacia

Yellow star thistle (Centaurea solstitialis), Russian knapweed (C. repens), and Malta star thistle (C. melitensis) all produce equine nigropallidal encephalomalacia by means of an unidentified toxin. Horses are the only species affected. The range for yellow star thistle includes California and Oregon and begins to extend eastward; Russian knapweed grows in Colorado, Utah, Wyoming, and Washington; and Malta star thistle is native to Texas. These plants are most abundant in nonirrigated pastures during summer and fall when other plants are dead, and plants retain their toxicity in hay. Low levels of consumption do not produce clinical signs, and poisoning requires continuous exposure and ingestion over several weeks. Once significant neurologic damage is clinically apparent, the course of the disease is irreversible. The first sign of poisoning is a sudden lack of coordination of the facial and oral movements required for effective eating or drinking, although the horse can swallow if food or water is placed at the back of the throat. It may attempt to drink by submersing its muzzle deeply into water. The facial muscles become hypertonic (fifth and twelfth cranial nerves),3 and a fixed facial expression is a characteristic sign, particularly when food is offered. There may be constant, although ineffective, chewing movements. The horse suffers weight loss and becomes depressed and inattentive, often with yawning, but is easily roused. The gait is usually normal early in the disease, with some aimless walking and circling; later, intermittent stiffness, slowness, ataxia, and proprioceptive deficits may occur. In prolonged cases, the horse develops a shuffling gait as a result of weakness, although its sensation and reflexes seem normal. Less impaired animals may survive for a while by scooping food, but complete recovery has not been observed, and affected animals eventually die of dehydration, starvation, or aspiration pneumonia. Horses of all ages may be affected, but younger horses are more susceptible to the disease (median age: 2 years). Occasionally, early in the disease, an animal shows signs more typical of encephalitis such as head pressing, walking through obstacles, excite-

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ment, or self-trauma, which subside after a few days. In a few cases, signs have been unilateral. Sharp cavitated areas of liquefactive necrosis of the substantia nigra and globus pallidus are pathognomonic for this disease, although if the animal dies at earlier than 7 days, these areas may only be discolored. Peak incidences of encephalomalacia occur in June through July and in October through November. Under experimental conditions, horses ate at least 60% and up to 200% of their body weight equivalent over 3 to 11 weeks to produce clinical signs.1· 3 · 8 · 13 Locoism

Locoweeds (some Astragalus spp and Oxytropis spp) grow in western North America from northern Mexico to southern Canada. Toxicity of the different species varies greatly, and some are not toxic. The compound that causes locoism is the indolizidine alkaloid swainsonine, which inhibits a-mannosidase, a lysosomal enzyme essential to cellular metabolism of oligosaccharides. Incompletely metabolized oligosaccharides accumulate in lysosomes and vacuoles, which resolve over a period of 10 to 14 days if consumption of the plant stops. Onset of clinical signs varies from as short as 2 weeks to as long as 2 months after beginning grazing. When locoweed has been consumed for 30 days or longer, cellular functions are disrupted in all tissues except skeletal and cardiac muscles. When locoweed is removed from the diet after this point, most tissues regenerate to some degree, but the brain and nerves are permanently damaged, and neurologic signs may even continue to progress. The neurologic signs that give the poisoning its name include depression, excitement when disturbed, trembling, ataxia, and behavioral unpredictability, causing the horse to be unsafe to ride and intractable for other work. Horses consuming locoweed lose weight as a result of impairment of the liver, pancreas, and thyroid and parathyroid glands. Other problems may include difficulty in eating and drinking, visual impairment, suppression of sexual activity, increased susceptibility to infection, abortion, and production of foals with limb deformities. The toxin is also transferred through the milk. Horses may die a convulsive death after excitation, die by misadventure, or starve. Although locoweeds are not highly palatable and they are not addictive,10 once horses start eating the plants, they typically must be removed from the source to stop consumption. As always, animals unfamiliar w ith the plants are more likely to be poisoned. There is no treatment for locoism except to remove horses from grazing infected areas well before there is permanent nerve damage.1• 2 , 6- 8 , 13 Some of the specific plants known to be involved in locoism include Astragalus lentiginosus (36 varieties), woolly loco (A. mollissimus [11 varieties]), garbancillo (A. wootonii [2 varieties]), A. thurberi, A. nothoxys, Oxytropis sericea, crazy weed (0. /ambertii), and 0. soximontana. Also incriminated are A. argillophilus, A. bisulcatus, and A. mollissimus var. earlei. 6· 13

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Convulsions

Western-whorled milkweed (Asclepias subverticillata) and the few other verticillate-leaved milkweeds contain neurotoxic cardenolides in their milky white sap instead of the related cardiotoxic cardenolides present in most Asclepias spp. The bitterness of the sap also makes the plants unpalatable, but horses eat them when the plants are baled into hay. Consumption of sufficient western-whorled milkweed causes central stimulation, convulsions, and rapid death. 11 A lethal dose is estimated at 0.05% of body weight dm in hay. Water hemlock or cowbane (Cictda maculata and other species) is a 5- to 10-ft tall umbillifer that grows only in wet swampy areas throughout North America. It is one of the most violently toxic plants known. Its most identifying characteristic is the thick rootstock at base of stem, divided horizontally into chambers containing yellowish oily liquid with the odor of raw parsnip. The yellow liquid extends up the lower parts of the hollow stem and contains cicutoxin, which acts as a violent convulsant directly on the central nervous system. The plant is much less toxic when baled into hay. The most toxic part of the plant is the rootstock. Most often, the plant is eaten as early growth in the spring. Ten to 60 minutes after ingestion, animals are apprehensive with dilated pupils, and slight muscle tics progress to contractions of major muscle groups. The strength of the convulsions then increases, and breathing becomes labored as the disease progresses. Death can occur as a result of anoxia within 30 minutes after a lethal dose, but animals that survive 5 or 6 hours usually recover with no lasting effects. Barbiturates have been used in treatment. 1, 6 • 8 Depression

Poison hemlock (Conium maculatum) is another 6- to 10-ft tall umbillifer that grows throughout North America, especially in ditches and along roadsides in cooler latitudes. The plant material smells of mouse urine, and a similar smell can be detected on the breath of poisoned animals. Early spring growth has the greatest palatability, and the plant is no longer toxic when dried in hay. The toxins are a series of piperidine alkaloids, including coniine, N-methyl conine, and others, whose concentrations change and increase as the plant matures. The alkaloids act similar to nicotine, first stimulating and then depressing autonomic ganglia and blocking the neuromuscular junction. Within 0.5 to 2 hours of consumption, animals seem apprehensive and then ataxic and weak in the rear. Normal corneal reflexes are retained, but awareness is lost. There is a weakened heart beat and coldness of extremities; animals become recumbent and comatose, and they die of respiratory failure. In severe cases, death occurs in 5 to 10 hours, but the intermittent coma can last several hours to 2 days in animals that recover. Four to five fresh leaves can poison a horse. 1• 6 · 8

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Black locust trees (Robinia pseudoacacia) grow throughout the eastern United States, bearing showy spikes of pink-throated white flowers in early spring. Some horses have been poisoned when tied to black locust trees, because they stripped and ate small amounts of its bark, and others have died after having access to trimmed or storm-felled branches.9 The toxic principal robin is a lectin or toxalbumin that acts as a central nervous system depressant and is present in throughout the plant. Its concentration in the bark fluctuates, with the highest levels in fall and winter. Clinical signs of black locust poisoning include depression, anorexia, weakness, dilated pupils, irregular tachycardia or diaphragmatic flutter, abdominal pain, and posterior paresis. Animals either survive or die within a few days, and treatment is symptomatic. 1• 6 • 8 • 9 • 13 The nightshades (Solanum spp) are mentioned in the Gastrointestinal section of this article. In horses, the propensity to colic makes this the major concern in nightshade poisonings. Nevertheless, it should be kept in mind that the solanine glycoalkaloids in this genus of plants can also cause neurologic signs, including depression, dyspnea, weakness, muscle trembling, and paralysis or convulsions before death. 1• &--s, 13 Jimsonweed or thornapple (Datura spp) is a robust annual growing 3 to 5 ft tall in disturbed soils over much of North America. Purplethroated, white showy flowers up to 4 in long are followed by fruits in spiny capsules. The plant contains the tropane alkaloids atropine and scopolamine, with the highest levels found in the seeds. Clinical signs of jimsonweed poisoning include anorexia, weight loss, rapid heart and respiratory rates, dilation of pupils, excessive thirst and urination, sweating, severe gastrointestinal atony, and abdominal pain. Horses have been poisoned by whole plants baled into hay as well as by the presence of 0.5% Datura seeds in grain. Removal of the plant material from the diet usually permits rapid recovery. 1• 6 Spinal Effects

Sudan, Johnsongrass, sorghum, and hybrids (Sorghum spp and hyb) grow throughout the southern United States and Mexico and are used heavily as forage and hay. Under conditions that are not well defined, a small proportion of horses eating sorghum forage or hay develop cystitis after several weeks to months. Most of the cases occur in grazing animals. Some degree of posterior ataxia is accompanied by urinary incontinence, for which the disease is named. The underlying lesion is axonal degeneration and demyelination of nerve fibers in the lumbar and sacral spinal cord. There is progression from dribbling urine and scalding dependent skin to complete rear paresis. The animal is alert and has no fever, with normal appetite, respiration, and heart rate. Mares may have continuous opening and closing of the vulva, with relaxation of the perineal muscles, and in male horses, the penis is relaxed and extended. The urinary bladder becomes distended and atonic, with moderate to severe cystitis, and ascending pyelonephritis

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frequently develops. Affected mares may abort, or foals may be born with multiple arthrogryposis. Affected horses may show gradual improvement over weeks to months with extensive supportive care once the source is removed, but complete recovery may not occur. Suggested mechanisms of intoxication include sublethal chronic exposure to hydrocyanic acid and the possibility that sorghums may contain lathyrogenic nitriles or their precursors. 1• 8 • 13 Singletary pea, caly pea, or wild winter pea (Lathyrus hirsutus) is a nutritious cool season forage whose seeds carry its toxin, which has not been identified. Horses eating hay with seedpods for weeks to months tend to stand with their hind legs too far forward. When forced to move, they walk in a stringhalt fashion with exaggerated stepping. Most recover when the hay source is removed, but complete recovery can take as long as several months. 1 · 6 • 7 Flatweed (Hypochoeris radicnta), also called false or summer dandelion, has been implicated in outbreaks of stringhalt in the Pacific Northwest.1· s. 7

CYANIDE

Relatives of plums and cherries (Prunus spp), including choke cherry, wild black cherry, and plum thickets, are found throughout North America. Many of these plants contain cyanogenic glycosides such as amygdalin (usually in fruit or pit) and prunasin (usually in leaves). When the plants are stressed by drought, frost, stunted growth, or wilting and are chewed and consumed by an animal, free cyanide is released into the stomach. Cyanide is rapidly absorbed into the bloodstream and blocks cytochrome oxidase in the tissues, preventing the uptake of oxygen. The blood turns cherry red as a result of undelivered oxygen, and the animal becomes dyspneic, with flaring nostrils, involuntary urination and defecation, trembling, ataxia, muscle contractions, prostration, struggling, and death minutes to hours after ingestion. 1 • 3• 8 Johnsongrass, Sudan, haygrazer, and their hybrids (Sorghum spp and hyb) also contain cyanogenic glycosides, and horses have been poisoned with cyanide by frosted sorghums in the same way. Unlike cattle, horses rarely consume enough sorghum to be poisoned by cyanide. Usually, a veterinarian arrives too late to treat the horse for cyanide poisoning, but the recommended therapy involves intravenous treatment with sodium nitrite and sodium thiosulfate. Nitrite binds hemoglobin to form methemoglobin, which reacts with free cyanide to form nontoxic cyanmethemoglobin. The enzyme rhodanese combines thiosulfate with cyanide to form thiocyanate, which is then eliminated in urine. 1 · 8

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SUMMARY

Horses poisoned by a plant may show a myriad of clinical signs. Awareness of the poisonous plants growing in a given area and those that are likely to appear in hay and their associated clinical signs can be instrumental in making diagnoses. More importantly, the information can be shared with clients to help prevent plant poisonings in horses. References 1. Cheeke PR: Natural Toxicants in Feeds, Forages, and Poisonous Plants, ed 2. Danville,

IL, Interstate Publishers, 1998 2. Correll OS, Johnston MC: Manual of the Vascular Plants of Texas. Renner, TX: Texas Research Foundation, 1970 3. Craig AM, Blythe LL, Roy ON, et al: Detection and isolation of neurotoxins from yellow star thistle (Centaurea solstitialis), the cause of nigropallidal encephalomalacia. In Colegate SM, Dorling PR (eds): Plant Associated Toxins: Agricultural, Phytochemical, and Ecological Aspects. Wallingford, CAB International, 1994, pp 257-262 4. Garland T, Bailey EM, Jr, Reagor JC, et al: Probable interaction between Solanum eleagnifolium and ivermectin in horses. /11 Ga rland T, Barr AC (eds): Toxic Plants and Other Natural Toxicants. Wallingford, CAB International, 1998, pp 423-427 5. Gay CC, Fransen S, Richards J, et al: Hypochoeris-associated stringhalt in North America. Equine Vet J 25:456-457, 1993 6. Kingsbury JM: Poisonous Plants of the United States and Canada. Englewood Cliffs, NJ: Prentice-Hall, 1964 7. Murphy M, Reagor J: Toxic plants. In Robinson NE (ed): Current Therapy in Equine Medicine, ed 4. Philadelphia, WB Saunders, 1997, pp 649-652 8. Oehme F: Plant toxicities. In Robinson NE (ed ): Current Therapy in Equine Medicine, ed 2. Philadelphia, WB Saunders, 1987, pp 672-682 9. Poppenga RH, Habecker PL, Barr AC, et al: Black locust (Robinia pseudoacacia) toxicosis in a group of Belgian draft horses. In Proceedings of the 41st Annua l Meeting of the American Association of Veterinary Laboratory Diagnosticians, Minneapolis, p 46, 1998 10. Ralphs MH, Panter KE, James LF: Grazing behavior and forage preference of sheep with chronic locoweed toxicosis suggest no addiction. Journal of Range Management 44:208-209 1991 11. Robinson GH, Burrows GE, Holt EM, et al: Investigation of the neurotoxic compounds in Asclepias subverticillata, western-whorled milkweed. In Garland T, Barr AC (eds): Toxic Plants and Other Natural Toxicants. Wallingford, CAB International, 1998, pp 435-439 12. Rowe LD, Norman JO, Corrier DE, et al: Photosensitization of cattle in southeast Texas: Identification of phototoxic activity associated w ith Cooperia pedunculata. Am J Vet Res 48:1658-1661, 1987 13. Schmitz DG: Toxicologic problems. In Reed SM, Bayler WM (eds): Equine Internal Medicine. Philadelphia, WB Saunders, 1998, pp 981- 1042 14. Spoerke DG, Jr, Smolinskie SC: Toxicity of Houseplants. Boca Raton, CRC Press, 1990, pp 25-28

Address reprint requests to A. Catherine Barr, PhD Texas Veterinary Medical Diagnostic Laboratory 1 Sippel Road College Station, TX 77843 e-mail: [email protected]