456
Equine vet. J. (2010) 42 (5) 456-459
Case Report
Trema micrantha toxicity in horses in Brazil
P. M. BANDARRA, S. P. PAVARINI, D. L. RAYMUNDO, A. M. R. CORRÊA, P. M. O. PEDROSO and D. DRIEMEIER*
Departmento de Patologia Clínica, Faculdade de Veterinária, UFRGS. Porto Alegre-RS, Brazil.
Keywords: horse; hepatotoxicity; hyperammonaemia; poisoning; Trema micrantha
Summary
After ingesting green leaves of T. micrantha, 2 horses showed
apathy, locomotor deficit, blindness, recumbency, paddling,
coma and death. The main gross findings were scattered
haemorrhages, enhanced lobular pattern of the liver, and
cerebral oedema. Histological changes included disseminated
haemorrhages, massive hepatocellular necrosis, neuronal
degeneration, Alzheimer type II astrocytes and cerebral
perivascular oedema. Clinicopathological findings which were
comparable with those observed in Trema micrantha poisoned
ruminants, associated with epidemiological evidence suggested
the diagnosis. Trema micrantha poisoning should be evaluated
as a possible cause in the diagnosis of equine hepatopathy and
occasional secondary encephalopathy.
Introduction
Many fast-growing pioneer trees compose the genus Trema
(Ulmaceae), some of which have been proved toxic to livestock.
Trema micrantha is widely distributed in South America, but it also
occurs in Central and North America. In Brazil, T. micrantha is
particularly abundant in woodland habitats or as secondary
vegetation in derelict areas (Pio-Correa 1984; Vasquez 1998). T.
micrantha has also been used as a pioneer tree in reforestation
systems, particularly for the recovery of burned or degraded soils
(Castellani and Aguiar 1998; Kissmann 1999). T. micrantha leaves
are palatable and readily consumed by cattle and other herbivores,
particularly in times of food shortage, occasions in which the plant
has been used as a source of forage (Kissmann 1999). The
suspicion of T. micrantha poisoning in livestock was derived from
field observations in the past decade of small south Brazilian goat
flocks and cattle herds. Subsequently, natural T. micrantha
poisoning has been observed in goats (Traverso et al. 2003) and the
experimental poisoning induced in rabbit, goats and cattle at doses
of 30, 35 and 50 g/kg bwt, respectively (Traverso and Driemeier
2000; Traverso et al. 2004). Poison peach or Trema tomentosa (T.
aspera), which has been shown to contain a trematoxin (Oelrichs
1968), has also been linked to poisoning in horses (Hill et al. 1985)
and other animals (Mulhearn 1942; Mcckenzie et al. 1985;
Trueman and Powell 1991). The clinicopathological syndrome in
*Corresponding author. Email: davetpat@ufrgs.br
[Paper received for publication 11.09.09; Accepted 01.10.09]
© 2010 EVJ Ltd
EQUINE VETERINARY JOURNAL
doi: 10.1111/j.2042-3306.2010.00035.x
evj_35 456..459
T. micrantha poisoning is characterised by hepatic insufficiency
due to hepatocellular necrosis (Traverso et al. 2003, 2004). On the
other hand, T. micrantha has been described as having analgesic,
anti-inflammatory and hypoglycaemic properties (Barbera et al.
1992; Schoenfelder et al. 2006). This communication describes
and discusses the clinical and pathological findings observed in an
outbreak of T. micrantha poisoning in horses.
Case history and clinical findings
The disease occurred at a ranch in southern Brazil, where 2 of 5
horses were affected and died. Animals were kept in a 2.5 hectare
paddock. Horses had been exclusively grazing at pastures. Natural
poisoning occurred due to the consumption of green leaves of the
branches of a T. micrantha tree (Fig 1A) that had fallen during a
storm 4 days before the outbreak. Branches of the plant showed
clear evidence that parts had been bitten off. A 6-year-old mare and
her 1-year-old colt were affected and showed locomotor deficit,
apathy, lateral recumbency, paddling, intermittent tonic
contractions of locomotor and neck muscles (Fig 1B), and coma.
The mare died 48 h after the onset of clinical signs and was
necropsied 11 h after death. In addition to the above described
clinical signs, the foal also went blind and remained recumbent and
unconscious for 8 days, when it was subjected to euthanasia in
extremis by i.v. injection of barbiturates and immediately
necropsied. The owner reported that the affected mare was the
dominant animal in the group.
Post mortem findings
Necropsy was performed in both horses and samples of multiple
tissues were collected, fixed in formalin, processed for histology
and stained using haematoxylin-eosin, periodic acid Schiff1 or oil
red2 method (Johnson 1992). Liver presenting as an enhanced
lobular pattern (Fig 1C), haemorrhages in subcutaneous tissues and
thyroid and adrenal glands, faeces covered by mucus and blood,
and mild to moderate cerebral oedema (Fig 1D) were the main
gross findings. Histological findings in the mare included
centrilobular hepatocellular necrosis associated with haemorrhage,
and moderate fatty hepatocellular degeneration in periportal areas
(Fig 2A). Severe subcapsular haemorrhage in the adrenal glands
P. M. Bandarra et al. 457

Fig 1: (A) Trema micrantha tree that had fallen during a storm. The subsequent access of horses to their leaves caused the poisoning. Insert: detail of the
plant. (B) Recumbent colt poisoned by T. micrantha during an episode of generalised tonic muscular contraction. (C) Liver from a T. micrantha poisoned
mare. Note enhanced lobular pattern. (D) Encephalon of a T. micrantha poisoned colt. Transverse section at the level of cerebellum and cerebellar
peduncules. Note oedematous white substance characterised by a yellowish colouration in circled areas of the cerebellar vermis (top) and pons (bottom).

Fig 2: (A) Liver of a T. micrantha poisoned mare. Severe centrilobular hepatocyte necrosis, moderate diffuse fat degeneration and severe diffuse hepatic
haemorrhage (haematoxylin and eosin, 40¥). (B) Cortex frontal from a T. micrantha poisoned colt. Capillary vessel showing extravasated plasma and
hyaline globules (arrowheads) and Alzheimer type II astrocytes (arrows) (periodic acid Schiff, 400¥).

and in the thyroid, and moderate diffuse congestion in heart,
kidneys and intestines were also seen.
The foal had severe diffuse hepatocellular fatty degeneration,
individual hepatocyte necrosis and multifocal ductal proliferation.
Cerebral cortex presented neuronal tumefaction with varying
numbers of Alzheimer type II astrocytes (Fig 2B). Additionally, all
levels of the brain and cerebellum had perivascular oedema
characterised by extravasated protein globules best visualised in
periodic acid Schiff stained sections (Fig 2B). In addition,
tumefaction and tubular necrosis were detected in the kidneys.
Refrigerated fresh samples of brain, cerebellum and cervical
spinal cord from both horses were analysed by direct
immunofluorescence of rabies, with negative results. Weak or
absent antiglial fibrillar acid protein3 immunostaining (1:500)
associated with positive immunostaining for S-100 protein3 (1:200)
performed on sections of cerebral cortex indicated the presence of
Alzheimer type II astrocytes (Summers et al. 1995).
Discussion
T. micrantha poisoning was suspected upon clinical and
pathological study of findings (Traverso et al. 2003, 2004)
associated with the presence of the plant in the paddock where
affected animals had been kept. Evidence that parts of the plant had
been bitten off and the absence of other known causes of
hepatotoxicity confirmed the diagnosis. The condition described
© 2010 EVJ Ltd
458
here may have been associated with monopolisation of the fallen
tree by dominant individuals, which therefore may have ingested
larger quantities of green leaves of T. micrantha as compared to the
other animals in the paddock. Certainly, the good palatability of T.
micrantha (Traverso et al. 2004) has played a role in the disease
described here. In Brazil, sporadic cases of hepatotoxicity in horses
have also been linked to the consumption of Senecio brasiliensis,
Crotalaria retusa and Brachiaria decumbens; however, none of
these plants has been associated with acute liver necrosis. On the
other hand, numerous plants may cause acute liver necrosis in
ruminants in Brazil (Tokarnia et al. 2002; Riet-Correa and Méndez
2007). Centrilobular hepatocellular degeneration and necrosis are
particularly common findings in association with hepatotoxic
insults and may be due to particularities of blood flow and high
enzymatic activity of the mixed-function oxidases in this region of
the hepatic lobule (Cullen 2007).
Haemorrhages may be secondary to the damaged liver due to
the excessive consumption of coagulation factors in necrotic insults
as well as to the inability to further synthesise coagulation factors
and platelets (Stalker and Hayes 2007). Neurological findings were
probably linked to hepatic encephalopathy and associated with the
action of neurotoxins, in particular ammonia, and possibly with
several other phenomena, such as alterations in neurotransmission,
permeability of the blood-brain barrier, and energy metabolism
(Häussinger et al. 2002). Astrocytes exhibiting signs of Alzheimer
type II degeneration, cerebral oedema and neuronal degeneration
have all been described in cases of hepatic encephalopathy
(Häussinger et al. 2002; Cullen 2007; Norenberg et al. 2009).
The foal affected by T. micrantha poisoning had been recumbent
and exhibited impaired consciousness for at least 8 days before the
decision on euthanasia was made; therefore, it may be said that the
animal could have survived longer. Except for the Senecio-
associated chronic disease in horses (Gava and Barros 1997), such a
long course of neurological failure due to hyperammonaemia has not
been seen with most of the Brazilian hepatotoxic plants (Tokarnia
et al. 2002; Riet-Correa and Méndez 2007). Affected animals
usually die sooner than that. Hepatic lesions were more severe in the
mare than in its foal, which showed mainly degenerative liver
changes, possibly manifested as a stage subsequent to the acute liver
damage. This animal probably remained recumbent due to
neurological deficit secondary to hyperammonaemia.
Nigropallidal encephalomalacia or ‘chewing disease’, a
clinically similar condition caused by the consumption of
Centaurea solstitialis (yellow star-thistle), affects horses in the
USA, Argentina and Australia (Humphreys 1988; Knight and
Walter 2001), but not in Brazil. Theiler’s disease, an acute and
sporadic hepatic disease of unknown aetiology, has not been
associated with acute hepatic necrosis and haemorrhage (Stalker
and Hayes 2007), changes usually seen in T. micrantha toxicosis.
Although cerebellar lesions in T. micrantha poisoning may
resemble those seen in cases of Fusarium verticillioides-induced
equine leukoencephalomalacia, malacia is the predominant change
induced by this mycotoxin-associated condition (Humphreys 1988;
Morgavi and Riley 2007). In addition, these horses had been fed
exclusively at pastures, in which there was no source of corn.
Furthermore, the vascular lesions observed in cases of
leukoencephalomalacia may also affect larger vessels (Maxie and
Youssef 2007) than those seen in cases of T. micrantha poisoning,
in which plasma exudation occurred only surrounding capillaries
and has not been associated with malacia. Finally, liver failure
caused by blue-green algal toxins (Humphreys 1988) is usually
© 2010 EVJ Ltd
Trema micrantha toxicity in horses
associated with a source of algae. Although field observations of T.
micrantha poisoning in Brazil have been linked mainly to goat
flocks, the present report indicates that special caution should be
taken when keeping horses in areas with T. micrantha.
Acknowledgements
This study was funded by The Coordenação de Aperfeiçoamento de
Pessoal de Nível Superior (CAPES) and Conselho Nacional de
Desenvolvimento Científico e Tecnológico (CNPq), Brazil.
Authors are grateful to Professor Cláudio Estêvão Farias da Cruz
for reviewing this manuscript.
Manufacturers’ addresses
1
Merck S.A., Rio de Janeiro, Brazil.
2
Sigma Chemical Co., St. Louis, Missouri, USA.
3
DAKO, Carpentaria, California, USA.
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Author contributions All authors contributed to the initiation,
conception and planning of this study. It execution was by P.M.B.,
S.P.P., D.J.R., A.M.R.C. and D.D. and the pathology and writing by
P.M.B., S.P.P., D.J.R. and D.D.

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