Page 916 - Equine Clinical Medicine, Surgery and Reproduction, 2nd Edition

Liver disease 891

VetBooks.ir cardiac insufficiency, indicating good bioavailabil- various species of plants (Fig. 5.17); for example,
different Senecio species may contain jacobine, jaci-
ity at least. Colchicine (0.03 mg/kg p/o) is a pyrro-
lizidine alkaloid that has been used for many years,
somewhat counterintuitively, as a potential hepatic dine, jacoline, jaconine, jacozine, senecionine,
senecivernine, seneciphylline, sencalenine, eruci-
antifibrotic drug in horses. Antioxidants are also foline, platyphylline, bulgarsenine and retrorsine;
suggested to help control of HSC activity and vita- while Cynoglossum species may contain viridiflorine,
min E (2–5 IU/kg daily) might be considered for this amabiline, rinderine, 7-angelylheliotridine, echina-
purpose. tine, 3’-O-acetylechinatine, heliosupine, heliosupine
N-oxide, acetylheliosupine and cynoglossamine.
Phlebotomy PAs are not themselves harmful to the horse but
Where iron accumulation is judged to be excessive must first be bioactivated by the cytochrome P450
and harmful, then repetitive phlebotomy may be system to toxic dehydropyrrolizidine alkaloids or
used to mobilise hepatic iron stores. Approximately pyrroles. Toxicity tends to be primarily manifest at
1.5 litres of blood per 100 kg BWT can be safely their site of biotransformation (i.e. the liver) where
removed every 1–2 weeks. Haematology can be they cross-link macromolecules such as DNA,
monitored alongside this and repeat biopsy is useful impairing mitosis and leading to characteristic meg-
to evaluate the impact on hepatic iron. alocytosis. Acute PA ingestion may result in acute
hepatocellular necrosis, with minimal inflammation
Prognosis and subsequent secondary portal fibrosis and bili-
The prognosis for recovery from hepatic insuffi- ary proliferation. Chronic ingestion may cause focal
ciency is invariably guarded at best as the condition hepatocyte necrosis with portal fibrosis and biliary
indicates a severe hepatic insult in all cases. Acute hyperplasia along with characteristic megalocyte
hepatic insufficiency cases may appear to show ini- formation.
tial recovery only to deteriorate as secondary fibrosis Although sometimes limited by palatability,
inevitably develops. ingestion still occurs perhaps due to individuals with
less selective appetites, poor grazing leaving horses
HEPATOTOXICITY more likely to eat less palatable plants and also incor-
poration into forages that may subdue any unpleas-
Definition/overview ant taste. In many areas, PA toxicity has become the
As the liver is the primary site of biotransformation most well-known cause of liver disease among horse
(detoxification) of noxious exogenous agents, hepa- owners and veterinarians and is often assumed to
totoxicity is a commonly encountered cause of liver be the cause of liver disease even when histopatho-
disease. Many different origins of hepatotoxins may logical confirmation has not been achieved. A recent
exist in horses including ingested plants, pharma- widespread and multifaceted investigation in the UK
ceutical and chemical agents and mycotoxins. indicated that ragwort (Senecio jacobea) was indeed
a very common weed but only a minority of horse
Aetiology/pathophysiology owners spent significant time trying to control it.
Given the multitude of plant species to which horses Despite this, findings on histopathology consistent
are exposed in pasture and in forage, it is not unlikely with PA toxicity were found in only 8% of biopsy
that hepatotoxic plants may be ingested by horses, specimens from clinical cases.
some of which may not be known or recognised. In addition to PA-containing plants, further
Several hundred plant species are known to contain hepatotoxicity has been associated with other plants
pyrrolizidine alkaloids (PAs) and many are commonly (Figs. 5.18, 5.19) including kleingrass (Panicum
seen in horse pastures around the world including coloratum), cocklebur (Xanthium sp.), Cestrum sp.,
many in the genera Senecio, Cynoglossum, Echium, Senna sp., Indigofera sp. and Lantana sp. Ingestion of
Crotalaria, Amsinckia, Symphytum, Chimonanthus red clover and alsike clover (Trifolium pratense and
and Heliotropium spp. Many different PAs exist in T. hybridum) is also associated with hepatotoxicity,