Toxicology Brief: Allium species poisoning in dogs and cats
Wild and domesticated Allium species have been used for culinary and ethnomedicinal purposes since the beginning of recorded history. About 95 species of native or cultivated leeks, chives, garlic, shallots, scallions, and onions are present in North America, and more than 80 ornamental Allium species are available. All Allium species and the products derived from them can be toxic to dogs and cats1; however, relatively few Allium species are of important toxicologic interest.
The domesticated species commonly involved in toxicosis include Allium cepa (onion), Allium porrum (leek), Allium sativum (garlic), and Allium schoenoprasum (chive). The plants form solitary or clustered bulbs and are strongly aromatic, with an onion or garlic odor when crushed. The distinctive aroma distinguishes Allium species from morphologically similar poisonous plants, particularly death camas (Zigadenus species).1
ToxicityAllium species contain a wide variety of organosulfoxides, particularly alk(en)ylcysteine sulfoxides. Trauma to the plants, such as chewing, converts the organosulfoxides to a complex mixture of sulfur-containing organic compounds. Many of these compounds or their metabolites are responsible for the odors, flavors, and pharmacologic effects of these plants. Many Allium species' organosulfur compounds appear to be readily absorbed through the gastrointestinal tract and are metabolized to highly reactive oxidants.2 Cooking or spoilage of Allium species does not reduce their potential toxicity.1
Mechanism of action
The primary toxicologic mechanism of Allium species-derived organosulfur compounds is oxidative hemolysis, which occurs when the concentration of oxidants in the erythrocyte exceeds the capacity of the antioxidant metabolic pathways. Catalase antioxidant activity in erythrocytes in dogs is low,3 and normal hemoglobin in cats is about two to three times more susceptible to oxidative damage than the hemoglobin in other species.4
Oxidation of the exposed beta-93 cysteine residues present in hemoglobin results in the formation of sulfhemoglobin.5 Sulfhemoglobin is less soluble than hemoglobin, so it precipitates, aggregates, and binds to the cell membrane and forms Heinz bodies. Other types of oxidation of hemoglobin globin chains result in membrane cross-linking reactions and eccentrocyte formation.6 The formation of Heinz bodies and eccentrocytes increases erythrocyte fragility and extravascular hemolysis. Direct oxidative damage to the erythrocyte cell membrane and its sodium-potassium pump or the oxidative production of hemin also contributes to cell lysis. Oxidation of the heme ion and associated methemoglobinemia results in a left shift of the hemoglobin-oxygen dissociation curve, decreased blood oxygen transportation capacity, and, ultimately, impaired delivery of oxygen to the tissues.
Thus, the result of the oxidative hemolytic process induced by Allium species consumption is the onset of anemia, methemoglobinemia, and impaired oxygen transportation. Although marked Heinz body formation may be present within a day after onions are ingested, the anemic nadir typically develops several days later.
Allicin and ajoene, pharmacologically active agents in garlic, are potent cardiac and smooth muscle relaxants, vasodilators, and hypotensive agents.7-9 Also, ajoene and other organosulfur compounds derived from onions are potent antithrombotic agents.10 Thus, hypotensive and antithrombotic effects can exacerbate the physiologic effects of anemia and impaired oxygen transportation. Garlic preparations that have not been aged cause direct damage to the gastric and ileal mucosa, resulting in pain and diarrhea.11
Exposure and susceptibility
Allium species toxicosis most commonly occurs after oral consumption. In addition to consuming fresh plant material, consuming juice, fresh and aged dietary supplements, powdered cooking preparations, dehydrated material, or food preparations derived from or containing Allium species can be potentially toxic to dogs and cats.1 Allium species toxicosis typically ensues after consumption of a single large quantity of the material or repeated small amounts. Dogs and cats are highly susceptible to onion toxicosis: Consumption of as little as 5 g/kg of onions in cats or 15 to 30 g/kg in dogs has resulted in clinically important hematologic changes. Onion toxicosis is consistently noted in animals that ingest more than 0.5% of their body weight in onions at one time.