CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
6PP, a prenylated flavonoid from Dalea elegans, inhibits mitochondrial respiration and induces mitochondrial-dependent cytotoxic activity
Autor/es:
CELENTANO AM, ISOLABELLA MP, ELINGOLD I, PEREZ C, CASANOVA MB, CABRERA JL, DIEZ RA, DUBIN M.
Lugar:
Buenos Aires
Reunión:
Jornada; VIII Jornadas Multisciplinarias de la Sociedad Argentina de Biología; 2006
Institución organizadora:
Sociedad Argentina de Biología
Resumen:
6PP, A PRENYLATED FLAVONOID FROM Dalea
elegans, INHIBITS MITOCHONDRIAL RESPIRATION AND INDUCES
MITOCHONDRIAL-DEPENDENT CYTOTOXIC ACTIVITY.
Celentano AM1, Isolabella
MP2, Elingold I3, Pérez C4, Casanova MB3,
Cabrera JL5, Diez RA2,
Dubin M3.
Dptos. 1Microbiología
y 2Farmacología, 3CEFYBO
UBA-CONICET, Fac. Medicina, 4Cát.
Farmacología, Fac. Odontología (UBA) y 5Farmacognosia, Fac.
Cs. Qcas. (UNC).
E-mail: amcele@fmed.uba.ar.
The
prenylated flavanone 2´-4´-dihidroxy-5´-(1´´´-dimethylallyl)-6-prenylpinocembrin
(6PP), obtained from the roots of Dalea elegans, shows antimicrobial
activity. Flavonoids depict multiple biological activities including
antioxidant effects and/or impairment of mitochondrial function. The aim of our
work was to evaluate mitochondrial toxicity of 6PP. When evaluating oxidative phosphorylation system in rat liver
mitochondria, 6PP (50, 100 μM) with malate-glutamate as substrate, stimulated O2 uptake
in state 4 and inhibited it in state 3 (p<0.05). When succinate was the
substrate, 6PP inhibited O2 uptake in state 4 at 100 μM (p<0.01) and inhibited it in
state 3 at concentrations 12.5-100 μM (p<0.01). As a result, in both conditions respiratory control
index values decreased at 6PP
concentrations 12.5-100 μM
(p<0.01). 6PP inhibited F0F1
ATPase activity in coupled mitochondria (37.2±6.5%-50 mM; 51.0±3.3%-100 mM; both p<0.01) and in submitochondrial
particles (46.2±6.0% 100 mM; p<0.01). To assess
cytotoxicity, MTT assay was employed. HEp-2 cells were incubated 24h with 6PP
in presence or absence of 0.5% albumin.
In the albumin-free group, 6PP was cytotoxic in a dose-dependent manner between
10 µM and 400 μM
(p<0.01). Albumin decreased 6PP
effect (inhibition of MTT reduction only at 200-400 μM, p<0.01), likely suggesting a lowered free
fraction. We conclude that this flavanone affects mitochondrial respiratory
chain and ATPase activity, inducing cytotoxic effects via mitochondrial damage.
Further studies are needed to complete this evaluation.