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.
MCT is experimentally used to cause pulmonary vascular syndrome in rats, which is
characterized by proliferative pulmonary vasculitis and pulmonary hypertension. MCT
intoxication is also used as a model for studies in pulmonary hypertension (Lamé et al.,
2000). LD50 is 109mg/kg in male rats (Mattocks, 1972).
In vitro experiments using endothelial cells of bovine pulmonary arteries showed that
MCTP reduced the capability of these cells to act as a permeable barrier and inhibited the
cellular proliferation. Apoptosis occurs in endothelial cells of pulmonary arteries when MCT
is in vivo administrated (Lamé et al., 2000).
Many studies have supposed that MCT acts in endothelial cells to cause pulmonary
hypertension. However, how these cells lose their functional capability is not known. MCTP
seems to react easily with thiol group of cistein and glutathione.
Auto-radiography analyses showed that MCTP binds covalently to specific proteins.
Lamé et al (2000) identified many proteins with targets for binding to MCTP, like: galectin-
1, PDI precursor (protein-disulfide isomerase), probably protein disulfide isomerase ER-60,
β- or γ-cytoplasmic actin and cytoskeletal tropomyosin. These proteins have functions which
are potentially important to maintain the barrier of endothelial cells.
6.2. Chemical Structure of PA
Alkaloids are compounds that have nitrogen in a heterocyclic ring and generally have
basic pH. They taste bitter, are physiologically and pharmacologically active and function as
a chemical defense of plants against herbivores. PA are a big group of alkaloids that contains
a pirrolizidine nucleus. They are widely spread, geographically and botanically. Many PA are
hepatotoxic, causing irreversible damage to the liver, while others are carcinogens (McLean,
1970; Cheecke, Shull, 1985; Prakash et al., 1999; Cheeke, 1988).
These alkaloids become toxic after bioactivation and metabolism in liver to yield a
dehydroalkaloid. These pyrrolic metabolites are potent alkylatins agents with short half-lives
in aqueous. Dehydroalkaloids have four pathways available for further metabolism:
hydrolysis to 6,7-dihydro-7-hydroxyl-1-hydroxymethyl-5H-pyrrolizide (DHP), alkylation of
cell macromolecules, release into the circulation, or conjugation with GSH to form 7glutathionyl-6,7-dihydro-1-hydroxy-methyl-5H-pyrrolizine
(GSDHP). DHP and GSDHP
have low toxicities compared to the parent dehydroalkaloid, so their formation can be
considered to represent detoxification. The distribution of metabolites between these
pathways determines both the sites at which toxicity is expressed and the degree of toxicity
(Mattocks, Jukes, 1990).
Lipidic peroxidation was examined by Griffin and Segall (1987) as a possible mechanism
of cell injuries caused by macrocyclic pyrrolizidine alkaloid of senecionine, a trans-4-OH-2hexenal,
isolated from rat hepatocytes. The results suggest that lipidic peroxidation that
occurs in presence of trans-4-OH-2-hexenal is not totally responsible for cell damages in rat
hepatocytes. Lamé and Segall (1986) showed that aldehyde dehydrogenase (ALDH) plays an
important role in detoxication of trans-4-OH-2-hexenal, one of the metabolites of PA formed
by lipidic peroxidation of membrane.