Natural toxins: Part 2 (Proceedings)

A lingering human impression that most synthetic chemicals/compounds are unsafe and those of natural origin are safe remains un-substantiated. Of an estimated 30,000 plant species (wild and cultivated) found in North America, approximately 700 species have been reported toxic to animals. These plants are toxic on account of chemicals found in them, which are toxic to animals on ingestions. These components (alkaloids, glycosides, phenols, phyto estrogens, resins etc.) are structurally and functionally diverse. Components of both Mushrooms and Fungi are equally diverse and cause toxicity in animals on ingestion. Veterinarians by training are not botanist but could be benefitted working with botanist (Taxonomist) in specimen Identifications.

This presentation discusses secondary metabolites (toxins) found in some plants, mushrooms and fungi which are reported toxic to pets. The young of the species seems more susceptible – curiosity. Treatment in most cases is at best symptomatic and supportive.

Sudden weakness and inco-ordination in animals following ingestion of some plant are suggestive of insult to either to the cardiovascular, nervous of musculoskeletal system,

Weakness and inco-ordination are suggestive of insults to either the cardiovascular, nervous or musculoskeletal system. Enzymes PK and LDH isozymes would be helpful in narrowing the differential.

Digitalis purpurea, Nerium oleander, convallaria majalis contain cardioglycocides compounds known to increase the force and contraction of the myocardium. In addition, such compounds cause cardiac blockage., Cardiac glycosides, by inhibiting the Na-K-Na K ATPase pump. This requires emergency treatment. Cardiac glycosides are found throughout the freshly cut and/or portions of the plants.

Convallaria majalis "Lily-of-the-Valley"

A perennial herb with slender running rootstock and leafless stem. Raceme of white bellshaped flowers. Fruits often ripen into red berries (seldom formed), a common flower garden plant, seldom eaten. Toxicity occasionally reported in Dogs,

Nerium oleander "Oleander"

An ornamental shrub of small densely branched tree. Leaves opposite or whorled, leathery, evergreen, elliptic with entire margin. Flowers are in terminal cluster, white, pink, red or yellow in color. All species including man are affected Very potent glycosides - 0.005-0.015% body weight causes death of animal.

Clinical signs: Severe gastroenteritis, increased pulse rate, bloody feces, vomiting, diarrhea, mydriasis, cardiac stimulation initially, followed by cardiac depression, coma and death (weakness, cold extremities).

Ricinus communis "castor-oil plant, castor bean, steadfast, wonder tree."

A large, robust annual or perennial woody herb with alternate, simple-palmately, lobed (7-9) and serrated leaves. Pungent odor when handled. Flowers are green and inconspicuous. The fruit is a three-lobed capsule with spiny exterior (three seeds per capsule). The seeds are large and mottled, usually a light brown (resembling engorged ticks).

Cannabis sativa "Mary Jane, Marijuana, Grass, Pot, Hashish, Indian hemp"

A course rough stemmed annual plant, formally cultivated for its fiber, is now widely used for medicinal and recreational purposes. It contains the mine altering compound tetrahydrocannabinol (THC) and closely related compounds, which affects all animal species including man. Pets are exposed by ingesting marijuana cigarette butts, human cancer medication, and/or marijuana prepared confectionaries.

Highly lipophilic, readily absorbed from the GI and respiratory paths. Slow in eliminating from the body – sequestered in body fat and undergoes entero-hepatic re-circulation.

Euphorbia sp. 'Spurge Family" E. pulcherrima (poinsettia), E. marginata (Snow-in-the-Mountain), E. splendens (Crown-of-Thorn), E. fulgen (scarlet plum), E. tirucalli (pencil tree).

Generalities: Produce a milky sap (all parts of the plant) that is irritating to the skin, eyes and (if eaten) the gastrointestinal tract.

Unknown toxic principle — possibly resins or glycoside. Mainly affects puppies and kittens.

Treatment – Symptomatic/Supportive

Family: Araceae Dieffenbachia: sp. "Dumbcane"

Fairly tall plants with fleshy stem girdled with leaf scars. Leaves are large with white or yellow spots.

Philodendron "P. andreanum (velour), P. erubescens (blushing), P. hastatum (elephant ears), P. pandiforme (fiddle leaf), P. micons (velvet-leaf), P. bipinnatifidum (tree)".

These plants are either climbers or erect with heart or arrow-shaped large, leathery leaves.

All parts are toxic. (Calcium oxalate crystals and unknowns).

Lilium longiflorum "Easter Lily"

Reported toxic to cats - ingesting the leaves of flowers: vomiting depression, polyuria, dehydration, and possible death from renal failure. Toxin - unknown. Indications of renal toxicity glucosuria, tubular epithelial casts, and proteinuria. Supportive/symptomatic treatment within

Phoradendron flavescens "Mistletoe"

Parasitic shrubs that grow on oaks or walnuts. Leaves are ovoid and opposite in arrangement on the stem. Fruits are white (especially toxic) - tea made from berries

Toxic principle — beta-phenylethylamine and tyramine (toxic proteins) and phoratoxin (a toxic lectin) which inhibits protein synthesis - all parts. Brought into homes around Christmas time when puppies and kittens come in contact.

Clinical signs: (1-2 hours following ingestion) - vomiting, profused diarrhea dilated pupil, rapid labored breathing, shock and death. Death due to cardiovascular collapse.

Treatment: Similar to that for severe gastroenteritis. Fluids and electrolyte replacements essential.

Colchicum autumnale "Autumn crocus"

All parts are toxic with colchicine and related alkaloids. Mitotic poison. (Interferes with cell division)

Alkaloid is cumulative and excreted in the milk (major excretory pathway)

Within hours (2-7) following ingestion, clinical signs characterized by throat burning, difficulty swallowing, abdominal pain, profuse vomiting and bloody diarrhea, shock and collapse. Death from respiratory failure. Kidney damage reported. - Very potent and long acting. Slow recovery.

Mushrooms.

Numerous species (approx. 5000) throughout the US; Small percentage (2%) reported to be toxic with < 12 species classified as deadly.

     Toxic Components – Chemically: not fully characterize

     Exposure is by ingestion. Whereas most mushrooms are edible and safe, a few contain diverse secondary metabolites (cyclopeptides, monomethylhydrazine, orelline/orellanin, muscarine, Ibotenic acid and muscimol, psilocybin, and unknowns) which on ingestion (humans and animals alike) result in mild to severe illnesses and even deaths. The mushroom species, most frequently implicated in all human/animal mushroom fatalities globally is Amanita phalloides. Time lapse (latent period) between ingestion of some poisonous mushrooms and observed clinical signs in animals so exposed, by and large dictates prognosis. Long delay time is synonymous with fatality. Short latent periods do not always indicate non-lethality since species of mushrooms ingested could be in combination rather than single species.

Mushroom species effecting clinical signs < 3h post ingestion, are from the genera Clitocybe, Inocybe, Chlrorophyllium, Russula, Psylocybe, Panaeolus, Paxillus and some Amanita and Conocybe to name a few. For the most part, their effects are self limiting and are not life-threatening. Those effecting clinical signs > 6h post ingestion are found in mushroom species of the genera Amanita, Galerina, Lepiota, and Conocybe, and are life-threatening. The sudden appearance of mushrooms and their short life span within the environment and to which animals have access create diagnostic challenges. History and time post ingestion at which clinical signs are observed determine treatment approach and prognosis. Animal's indiscriminate eating habits, make establishing such time difficult to impossible. With no proven antidotes for treating mushroom poisonings, treatment is by and large directed at decontamination, mushroom identification when possible, and intensive supportive care.

Incidences of mushroom poisoning in both human and animal are low. In too large a percentage of suspected mushroom poison cases, the implicated mushroom is not adequately identified. Few mycetismus-induced fatalities are reported, and, that most cases are managed with symptomatic and supportive care is also contributing factors. With the indiscriminate eating habits of animals, the sudden appearance and short life-span of mushrooms within the environment, and to which animals have access, higher incidence in animals should be the expected. More efforts need to be directed at addressing Mushroom species' identification, their toxins, patho-physiology, diagnosis, and treatment protocols. In so doing, reported incidences would be more meaningful.

Aflatoxins /Aflatoxicosis

Hepatotoxic in many animal species – Dogs, cats, other species including man

Dogs are highly susceptible

Lower hepatocellular glutathione (GSH) concentrations

Differences in activity of GSH-S-transferase

Consumed food ≥ 60 ppb - problematic

Clinical Sign

Sudden death", Anorexia, Lethargy, Vomiting, Jaundice, Diarrhea, Abdominal effusion

Clinical Pathology

Coagulopathies, Electrolyte disturbances, Hypoalbuminemia, Increased liver enzyme activities, Hyperbilirubinemia (> 2.5 mg/dL), Hypocholesterolemia, Stress leukogram – often absent

Pathology

Hepatomegaly, Hepatic cytoplasmic vacuolation, Binucleate or multinucleate periportal hepatocytes, Hepatocyte necrosis, Biliary epithelium hyperplasia

Mycotoxins: Penitrem-A and Roquefortine C

Mycotoxins (secondary fungal metabolites), reported in association with sustained dose dependent tremors in animals (dogs) having ingested garbage - moldy feeds (primarily dairy products) two hours prior Species of the genera Penicillium are implicated

Clinical signs

Vomiting, tremors progressing to seizures and left untreated, death.

Pathophysiology

Inhibition of inhibitory neurotransmitters, glycine and Gamma-aminobutyric Acid (GABA)

Diagnosis

History of exposure to moldy garbage (dairy products), Clinical signs and response to treatment. Sample – stomach contents, vomitus, suspected feed - analysis

Differential diagnosis

Strychnine, metaldehyde, ethylene glycol, cholinesterase inhibitors, methylxanthines, pseudoephedrine hydrochloride, cocaine

Treatment

Control tremors and seizures with Diazepam, methocarbamol or pentobarbital; Diazepam + methocarbamol combination Following tremors/seizures control, institute GI decontamination procedure – gastric lavage, activated charcoal, cathartic, and supportive therapy – IV fluids, corticosteroids and temperature control

Prevention

Discourage dogs from ingesting moldy garbage