• Acute or chronic liver failure caused by ingestion of plant, particularly those containing pyrrolizidine alkaloids Toxicity: pyrrolizidine alkaloid, iron overload, mycotoxins, heavy metals, agrochemicals, drugs, cyanobacteria and hyperlipemia.
• Cause: ingestion of toxins
• Signs: signs of acute or chronic liver disease including anorexia, weight loss, ventral edema, depression, icterus +/- signs of hepatic encephalopathy, eg apparent blindness, circling, head-pressing; respiratory distress.
• Diagnosis: serum chemistry analysis, complete blood count, hepatic ultrasound examination, liver biopsy, analysis of serum/feed/water for toxins.
• Treatment: supportive therapy, removal of inciting cause.
• Prognosis: dependent on underlying cause.

Print off the factsheet on Pasture management and Poisonous plants – what to look out for to give to your clients.

• Chronic liver disease most common Liver disease: overview – characterized by weight loss Weight loss: overview, anemia, jaundice and encephalopathy Liver: hepatoencephalopathy.
• Acute disease rarer – characterized by encephalopathy.

• Worldwide, although certain plants are geographically limited to specific areas, eg:
  • USA: ragwort Ragwort (Senecio jacobaea), crotalaria and tarweed poisoning (‘walking disease’), Senecio spp (all over USA), Crotolaria spectabilis (Southern States of USA), Gynoglossum officinale (Western USA).
  • Australia: crotalaria poisoning (‘Kimberley horse disease’; ‘walkabout’).
  • New Zealand: ragwort poisoning (‘Winton disease’).
  • South Africa: ragwort and crotalaria poisoning (‘dunsiekte’).
  • Australia: heliotrope and echium poisoning (‘walkabout’ disease).
  • UK: ragwort poisoning.
  • Germany: schweinsberger brankheit.
  • Russia: suiljut disease.
  • Canada: pictou disease.
  • South Africa: jaagsiekte; Crotalaris spp poisoning.
• Blue-green algae toxicosis Toxicity: blue-green algae is more prevalent in summer months and hot climates.

• Iron toxicity Toxicity: iron occurs in young foals (<3 days old).

• Cost of treatment.

• Hepatic metabolism of drugs will be altered.

• Hepatotoxic plant species include Senecio spp, Lupinus, Heliotropium, Echium, Symphytum, Crotalaria, Trichodesma, Amsinckia, Cynoglossum, Panicum and Trifolium hybridum and T. pratense:
  • Many of these contain pyrollizidine alkaloids Toxicity: pyrrolizidine alkaloid, with Senecio spp being the most commonly implicated in equine hepatic disease in Europe.
  • Senecio spp are generally unpalatable and are typically only consumed when other food is unavailable, or when palatability increases following droughts or frost:
    • As PA retain their toxicity in dried forages, toxicity may occur when horses ingest plants within conserved forages, or when the plants are cut and left on pasture.
    • All parts of the Senecio plant contain PA, with levels being highest at the onset of flowering.
  • Chronic liver disease Liver disease: overview has been reported in horses in Texas grazing pasture planted in Klein grass (Panicium coloratum) and also horses fed Klein‐grass hay. The toxic component is thought to be a saponin.
• Liver disease occurs with ingestion of mycotoxins, particularly fumonisin B1 in stored forage:
  • More than 30 fumonisins have been described, being produced by Fusarium verticillioides, F. proliferatum, other Fusarium spp and Aspergillus niger, A. flotixins and sterigmatocystin are also implicated.
• Animals lack an efficient mechanism to eliminate iron from the body, with only small quantities of iron being eliminated via loss of blood, sweat, intestinal epithelial cells, skin and urinary cells:
  • Consequently, abnormalities in iron homeostasis can cause significant iron overload.
  • Hepatic and systemic iron overload is a common finding in many advanced liver disorders in horses. In most cases this is a secondary consequence of underlying liver disease attributable to abnormal iron homeostasis, in part because of reduced hepatic synthesis of hepcidin which leads to uncontrolled intestinal iron absorption.
  • Less commonly, iron accumulation is due to primary iron overload, with the hepatic iron accumulation leading to secondary hepatic disease.
  • Primary iron overload may occur with excess dietary iron intake, parenteral administration of excess quantities of iron, and possibly with hemolytic disorders and repeated blood transfusions.
• Hyperlipemia Hyperlipemia is a very common cause of liver failure, particularly amongst insulin dysregulated native breed ponies, miniature breeds and donkeys:
  • Negative energy balance and increased levels of stress hormones trigger lipolysis of triglycerides in adipose tissue, with resultant increases in circulating free fatty acids, triglycerides and lipoproteins.
  • Upregulation in the activity of lipoprotein lipase, which converts triglycerides to free fatty acids to be used as energy substrates or to be stored in adipose tissue, fails to clear circulating triglycerides.
  • Deposition of lipid within organs leads to multi-organ failure including liver failure.
• Exposure to carbon tetrachloride, chlorinated hydrocarbons, hexachloroethane, carbon disulfide, arsenic, monensin, pentachlorophenols, phenol, paraquat, halothane (goats, llamas), isoflurane, phenobarbital, tannic acid, copper disodium edetate, and high doses of ivermectin may cause centrilobular necrosis and hepatic failure:
  • Phosphorus causes primarily periportal changes. Changes from active hepatitis to cirrhosis may occur after use of isoniazid, nitrofuran, halothane, aspirin, or dantrolene in large animals.
  • Erythromycin, rifampin, anabolic steroids, phenothiazine tranquilizers, some diuretics, quinidine sulfate, and diazepam have been associated with cholestasis and icterus Liver: icterus.
• Blue-green algae poisoning Toxicity: blue-green algae occurs when horses ingest a toxic dose of cyanobacteria:
  • Cyanobacteria, commonly referred to as blue-green algae, are a group of bacteria that live in aquatic ecosystems, eg ponds, lakes, and creek.
  • Horses living in proximity to farmland and industrial areas are more likely to enter into contact with contaminated waters.
  • Cyanobacteria can produce two distinct kinds of toxins: hepatotoxins and neurotoxins.
  • Ingestion can occur when horses swim in, or drink from waterways contaminated with toxic algae.

Specific

• Ingestion of toxic plants, mycotoxins or cyanobacterial toxins.
• Excess dietary iron intake or parenteral administration.
• Factors that predispose to hyperlipemia Hyperlipemia.
• Exposure to hepatotoxic chemicals / drugs.

• Pyrrolizidine alkaloids Toxicity: pyrrolizidine alkaloid are protoxins which are converted by hepatic CYP450 enzymes into highly reactive derivatives which react with macromolecules (eg proteins, nucleic acids and lipid) in hepatocytes and hepatic endothelial cells. This inhibits protein synthesis and induces oxidative stress and lipid peroxidation. DNA damage inhibits hepatocyte mitosis, preventing hepatocyte regeneration, leading to megalocytosis and fibrosis.
• High doses of fumonisins cause liver pathology and mild cerebral lesions, while chronic, lower-level exposure causes predominantly leukoencephalomalacia Neurology: mycotoxic leukoencephalomalacia. Hepatic disease is characterized by hepatic lobular necrosis, hepatocyte vacuolation, centrilobular fatty change, periportal fibrosis, periportal vacuolation, bile duct proliferation and mild mononuclear infiltrate.
• Accumulation of iron within the liver, whether primary or secondary to liver disease, can exacerbate liver disease and fibrosis via production of reactive oxygen species through the Fenton and Haber–Weiss reaction.
• Accumulation of lipid within the liver results in organ failure.

• Pyrrolizidine alkaloids Toxicity: pyrrolizidine alkaloid have a cumulative effect, with chronic, cumulative toxicity being the most common scenario, although there is typically an acute onset and rapid deterioration in clinical signs as hepatic failure ensues. Experimental challenge with Senecio vulgaris at 10% of diet resulted in failure around 5-7 months.

Refereed papers

• Recent references from PubMed and VetMedResource.
• Moore R E, Knottenbelt D, Matthews J B et al (2008) Biomarkers for ragwort poisoning in horses: identification of protein targets. BMC Vet Res 4, 30 PubMed.
• Pearson E G (1999) Liver disease in the mature horse. Equine Vet Educ 11, 87-96 VetMedResource.

UK

• For further information and advice on Ragwort contact Rachel Molloy at The British Horse Society on +44 (0)1926 707807 or r.molloy@bhs.org.uk.