Artículo
Abstract The prenylated flavanone 2'-4'-dihidroxy-5'-(1" '-dimethylallyl)-6-prenylpinocembrin) (6PP), isolated from the roots of Dalea elegans, shows antimicrobial activity. The aim of this study was to evaluate mitochondrial toxicity and antioxidant properties of 6PP. Addition of micromolar concentrations of 6PP to rat liver mitochondria, stimulated O2 uptake in state 4 and inhibited it in state 3 when malate-glutamate was the respiratory substrate, and inhibited O2 uptake in state 3 when succinate was the substrate. Highest concentration of 6PP also inhibited O2 uptake in state 4 in the latter case; in both conditions, respiratory control index values were decreased. This flavanone collapsed the mitochondrial membrane potential in a concentration-dependent manner. 6PP also inhibited F0F1-ATPase activity in coupled mitochondria and in submitochondrial particles. In the latter, this compound also inhibited NADH oxidase and succinate dehydrogenase activities. HEp-2 cells were incubated for 24 h with 6PP in presence or absence of 0.5% albumin. As measured by reduction of the mitochondrial-related probe MTT, in the albumin-free condition, 6PP was cytotoxic in a concentration-dependent manner; on the other hand, albumin decreased 6PP effect. In addition, in rat liver microsomes 6PP: (1) inhibited the enzymatic lipid peroxidation, (2) exhibited significant scavenging activity, measured by DPPH reduction assay and (3) demonstrated significant antioxidant activity by decreasing the reduction of Mo(VI) to Mo(V). We suggest that 6PP impairs the hepatic energy metabolism by acting as mitochondrial uncoupler and by inhibiting enzymatic activities linked to the respiratory chain. 6PP also exerts both antioxidant and antiradical activities. Due to its cytotoxicity, this molecule, and its future structure developments, can be considered as a potentially promising therapeutic agent, for instance in cancer chemotherapy. The prenylated flavanone 2 -4 -dihidroxy-5 -(1-dimethylallyl)-6-prenylpinocembrin) (6PP), isolated from the roots of Dalea elegans, shows antimicrobial activity. The aim of this study was to evaluate mitochondrial toxicity and antioxidant properties of 6PP. Addition of micromolar concentrations of 6PP to rat liver mitochondria, stimulated O2 uptake in state 4 and inhibited it in state 3 when malate–glutamate was the respiratory substrate, and inhibited O2 uptake in state 3 when succinate was the substrate. Highest concentration of 6PP also inhibited O2 uptake in state 4 in the latter case; in both conditions, respiratory control index values were decreased. This flavanone collapsed the mitochondrial membrane potential in a concentration-dependent manner. 6PP also inhibited F0F1-ATPase activity in coupled mitochondria and in submitochondrial particles. In the latter, this compound also inhibited NADH oxidase and succinate dehydrogenase activities. HEp-2 cells were incubated for 24 h with 6PP in presence or absence of 0.5% albumin. As measured by reduction of the mitochondrial-related probe MTT, in the albumin-free condition, 6PP was cytotoxic in a concentration-dependent manner; on the other hand, albumin decreased 6PP effect. In addition, in rat liver microsomes 6PP: (1) inhibited the enzymatic lipid peroxidation, (2) exhibited significant scavenging activity, measured by DPPH reduction assay and (3) demonstrated significant antioxidant activity by decreasing the reduction of Mo(VI) to Mo(V). We suggest that 6PP impairs the hepatic energy metabolism by acting as mitochondrial uncoupler and by inhibiting enzymatic activities linked to the respiratory chain. 6PP also exerts both antioxidant and antiradical activities. Due to its cytotoxicity, this molecule, and its future structure developments, can be considered as a potentially promising therapeutic agent, for instance in cancer chemotherapy.
Mitochondrial toxicity and antioxidant activity of a prenylated flavonoid isolated from Dalea elegans
Elingold, Igal
; Isollabella, M. Paula; Casanova, Marta Beatriz
; Celentano, Ana M.; Perez, Cristina del Carmen; Cabrera, Jose Luis
; Diez, Roberto Alejandro; Dubin, Marta
Fecha de publicación:
02/2008
Editorial:
Elsevier Ireland
Revista:
Chemico-biological Interactions
ISSN:
0009-2797
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Palabras clave:
ANTIOXIDANT
,
FLAVONOID
,
MITOCHONDRIAL
,
TOXICITY
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(CCT - CORDOBA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - CORDOBA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - CORDOBA
Articulos(CEFYBO)
Articulos de CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Articulos de CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
Elingold, Igal; Isollabella, M. Paula; Casanova, Marta Beatriz; Celentano, Ana M.; Perez, Cristina del Carmen; et al.; Mitochondrial toxicity and antioxidant activity of a prenylated flavonoid isolated from Dalea elegans; Elsevier Ireland; Chemico-biological Interactions; 171; 3; 2-2008; 294-305
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