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Medicinal Plants Classification Biosynthesis and ... - Index of

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Pharmacologic Study <strong>of</strong> Some Plant Species from The Brazilian Northeast<br />

Monocrotaline (MCT) (Figure 3) is the main PA found in plants <strong>of</strong> Crotalaria genus.<br />

Although it is a hepatotoxic alkaloid, pneumotoxic, nefrotoxic, cardiotoxic, teratogenic <strong>and</strong><br />

carcinogenic effects were also related (Mattocks, 1986; Thomas et al., 1996; Ribeiro et al.,<br />

1993; Cheecke, 1998; Medeiros et al., 2000; Kosog<strong>of</strong> et al., 2001).<br />

The main alteration observed in lungs are edema <strong>and</strong> congestion, with consolidated areas<br />

in parenchyma, causing interstitial <strong>and</strong> arteriolar lesion, inflammation, hemorrhage <strong>and</strong><br />

fibrosis (Gardiner et al., 1965; Newberne, et al., 1974; Nobre et al., 1994; Baybutt, Molteni,<br />

1999; Baybutt et al., 2002; Copple et al., 2002).<br />

Figure 3. MCT molecule.<br />

Schraufnagel (1990) studied lungs <strong>of</strong> rats treated with monocrotaline. He observed<br />

formation <strong>of</strong> new blood vessels, which occurs on pleural surface <strong>and</strong> on bronchovascular tree,<br />

but not in alveolar capillaries, suggesting that these capillaries answer in different ways to<br />

these angiogenic stimuli.<br />

Deaths can occur due to damage on kidneys (Jubb et al., 1993). The main alterations are<br />

tubular damage <strong>and</strong> glomerulonephritis (Hayashi, Lalich, 1967; Carstens, Allen, 1970;<br />

McGrath et al., 1975; Figueredo et al., 1987).<br />

Hepatocytes show citoplasmatic <strong>and</strong> nuclear gigantism (megalocytosis) (Bull, 1955;<br />

Cheeke, Shull, 1985; Mattocks, 1986; Thomson, 1990; Jubb et al., 1993). Other lesions are<br />

progressive fibrosis, bile ducts proliferation (Cheeke, Shull, 1985; Mattocks, 1986; Thomson,<br />

1990) <strong>and</strong> occlusion <strong>of</strong> veins (Cheeke, Shull, 1985; Mattocks, 1986). There is impairment <strong>of</strong><br />

metabolic liver functions. The levels <strong>of</strong> serum proteins are diminished due to the reduction in<br />

protein synthesis (Mir<strong>and</strong>a et al., 1980), causing ascites <strong>and</strong> edema (Cheeke, Garman, 1974).<br />

In liver, MCT is first activated to an electrophilic compound named monocrotaline<br />

pirrole (MCTP). It can also be named dehydromocrotaline (DHM), which have characteristics<br />

<strong>of</strong> a bifunctional agent <strong>of</strong> crossed linkage <strong>and</strong> has half-life period <strong>of</strong> 3s in aqueous with pH<br />

next to neutral. Stabilization <strong>of</strong> MCTP by red blood cells makes the transport to the liver<br />

easier. The evidences <strong>of</strong> the involvement <strong>of</strong> pulmonary endothelium in MCT intoxication is<br />

supported by the similarity between hepatic <strong>and</strong> pulmonary endothelium, evidence <strong>of</strong><br />

thymidine increase (or deoxythymidine) <strong>and</strong> reduction <strong>of</strong> 5-hydroxitriptamine removed by<br />

endothelial cells <strong>and</strong> outflow <strong>of</strong> macromolecules. In primary pulmonary hypertension,<br />

disturbs on endothelial cell surface are suspects <strong>of</strong> being the initial factor to the formation <strong>of</strong><br />

platelet aggregation <strong>and</strong> cause thrombosis in situ (Lamé et al., 2000).<br />

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