Medicinal Plants Classification Biosynthesis and ... - Index of

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S.M.M. Vasconcelos, J.E.R. Honório Júnior, R.N.D. Cavalcante de Abreu et al.
Nobre et al., 2004 a,b). Necropsy findings are typical of chronic liver disease. The liver is
hard, increased in volume (Gibbons et al., 1953; Gardiner et al., 1965; Nobre et al., 1994;
Arzt, Mount, 1999) and of nutmeg looking (Arzt, Mount, 1999). In lungs, the main
alterations observed were edema, congestion and consolidated areas of parenchyma (Gardiner
et al., 1965; Nobre et al., 1994). Histologically, the mains findings occurred in liver: fibrosis,
hepatomegalocytosis (Gibbons et al., 1953; Gardiner et al., 1965; Arzt, Mount, 1999),
necrosis (Gardiner et al., 1965), vacuoles on hepatocytes (Nobre et al., 1994), hemorrhage
(Arzt, Mount, 1999) and, sometimes, proliferation of biliar ducts (Gardiner et al., 1965; Arzt,
Mount, 1999). The lungs may present diffuse fibrosing alveolitis with thickening of
interalveolar septs, edema and mononuclear inflammatory infiltrate and, mainly, foam cells
(Gardiner et al., 1965; Nobre et al., 1994). Horses exposed to metabolic and nutritional stress
during dry season, hard working or pregnancy are more susceptible to be affected by the
disease (Curran et al., 1996). The chronic disease is the usual form of intoxication, and the
clinical signs manifest weeks or months after eating the plant. The liver injuries are
progressive and the death may occur months or years after ingestion of plant that contains PA
(Cheeke, 1998).
Nobre et al (2005) reported an outbreak of acute intoxication by C. retusa of 80 sheeps.
Anorexia, severe depression, mild jaundice, incoordination and recumbence were observed in
16 sheep that died within 12 h. The liver had a nutmeg appearance at necropsy and
centrilobular necrosis was observed at histology. In order to reproduce the symptoms, seeds
of C. retusa were given to six sheep at doses of 2.5 (two sheep), 5, 10, 20 and 40 g/kg (one
sheep for each dose). Clinical signs and gross and histological lesions were similar to those
observed in field outbreak. Nobre et al (2004b) observed the same symptoms in horses and
asininos intoxicated with the seeds of C. retusa. The necropsy revealed type II Alzheimer
astrocytes, isolated or in groups mainly in caudate nucleus and cortex.
Barreto et al (2006) demonstrated that MCT has a direct in vitro effects on astrocyte
primary culture, interfering on cellular growth and inducing morphological changes, and
suggests that the astrocytes‘ response to this alkaloid may be related to CNS damages and
neurological signs sometimes showed by Crotalaria intoxication in animals. Low doses of
dehydromonocrotaline show astrogliotic reaction. At higher concentrations (10-500 microM),
astrocytes shrank their bodies and retracted their processes, presenting a more polygonal
phenotype and a weaker expression on GFAP labelling nuclear chromatin, revealed
condensed and fragmented chromatin in an important proportion (+/-30%), suggesting signs
of apoptosis (Barreto et al., 2008). Signs of apoptosis were also observed at low and high
doses of MCT in endothelial cells of pulmonary arteries (Thomas et al., 1998).
Studies with cultures of endothelial pulmonary vascular cells of rats (RECs) show that
MCTP caused a delayed and progressive release of lactate dehydrogenase from REC
monolayers. Progressive cell detachment was evident and remaining cells became enlarged.
Morphologic changes included cytoplasmic vacuolization, prominent stress fibers and
nuclear enlargement. In addition to structural changes, MCTP inhibited cell proliferation at
concentration of 0.05µg/ml. DNA crosslinking was evidenced at 24 and 48 hours posttreatment.
Hoorn et al (1993) suggest, with this article, that MCTP is directly toxic to these
cells. The cytostatic nature of the compound, in combination with its cytolytic effect on