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Advisor(s)
Abstract(s)
2-Styrylchromones are a novel class of chromones,
vinylogues of flavones (2-phenylchromones),
which have recently been found in nature. The best described
property of almost every group of flavones and
other flavonoids, especially the hydroxylated derivatives,
is their capacity to act as antioxidants. Indeed there is a
widely accepted view that the positive health effects of
flavones are due to their antioxidant activity. As oxidative
stress is a main cause of liver toxicity induced by
several hepatotoxicants, agents with the ability to protect
the liver against reactive pro-oxidant species may be
therapeutically useful. The present study evaluated the
possible protective activity of six new synthetic polyhydroxylated
2-styrylchromone derivatives against the
pro-oxidant hepatotoxicity exerted by tert-butylhydroperoxide
(t-BHP) in freshly isolated rat hepatocytes.
The cells were preincubated with the 2-styrylchromones
in the final concentrations of 3.125, 12.5, 25, 50, 100, and
200 lM for 5 min before treatment with 1.0 mM t-BHP
for 30 min (throughout this incubation period the cells
were exposed to both compounds). The well-known
antioxidant 3-hydroxyflavone (quercetin) was used as
positive control. At the end of the 30-min incubation
period, aliquots of cells suspensions were taken
for measurement of lactate dehydrogenase leakage,
thiobarbituric acid reactive substances, reduced glutathione,
and oxidized glutathione contents. The tested
compounds exhibited in vitro protective activity against
t-BHP induced hepatotoxicity (1.0 mM, 30 min). Three
of the tested compounds, at the concentrations of 3.125,
12.5, 25, and 50 lM, prevented the t-BHP induced glutathione
depletion, lipid peroxidation, and cell death in
freshly isolated rat hepatocytes to a comparable potency
with that of quercetin.
Description
Keywords
2-Styrylchromones tert-Butylhydroperoxide Hepatoprotective activity Freshly isolated rat hepatocytes
Citation
Fernandes, Eduarda; Carvalho, Márcia; Carvalho, Félix; Silva, Artur; Santos, Clementina; Pinto, Diana; Cavaleiro, José; Bastos, M Lourdes (2003). Hepatoprotective activity of polyhydroxylated 2-styrylchromones against tert-butylhydroperoxide induced toxicity in freshly isolated rat hepatocytes. Archives of Toxicology. ISSN 0340-5761. 77:9, p. 500-505