CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Trypanocidal napthoimidazoles: studies on mitochondrial rat liver toxicity and mutagenicity
Autor/es:
CASANOVA MB,ELINGOLD I, CELENTANO AM, DE CASTRO SL, DUBIN M
Lugar:
Buenos Aires, Facultad de Medicina ,UBA
Reunión:
Congreso; Sociedad Argentina de Farmacología Experimental; 2007
Institución organizadora:
Sociedad Argentina de Farmacología Experimental
Resumen:
Trypanocidal
naphthoimidazoles: Studies on mitochondrial rat liver toxicity and mutagenicity
Casanova MB,
Elingold I, Celentano AM1, Menna-Barreto R2,
Ventura-Pinto A3, Chan A4, Nagel R4, de Castro
SL2, Dubin M. CEFYBO UBA-CONICET, Dptos.
1Microbiología, Fac. Medicina,2Instituto Oswaldo Cruz, 3Universidade
Federal do Rio de Janeiro, Río de Janeiro, Brasil, 4
INAME-Ministerio de Salud.
dubin @mail.retina.ar
Naphthoimidazole (NPH)
derivatives from β-lapachone:
N1, N2 and N3, were shown to have important trypanocidal activity. The aim of
this study was the evaluation of the mitochondrial rat liver toxicity and the
potential mutagenicity of these compounds. It was found that N1 and N3 (25 and
50μM) produced a significant increase in oxygen uptake with succinate (site II
substrate) and mitochondria in metabolic state 4 (resting respiration). On the
other hand, state 3 (active respiration) was not modified. Also the respiratory
control index (RCI) decreased significantly in the presence of either N1 (25
and 50μM) or N3 (10, 25 and 50μM). Mitochondrial membrane potential (MMP) was
measured by rhodamine 123 fluorescence with
malate-glutamate as substrate.
Both, N1 (50μM) and N3 (50 μM) decreased significantly this parameter
after 25 min. incubation 69,9 and 72,8 %, respectively. N2 addition did not
significantly modify the respiratory states, RCI or MMP. None of the three NPH
was found to be mutagenic when assayed with the Salmonella/microsome test. From these results it can be concluded that
of the three NPH studied, N2, because its lack of toxicity, can be considered
as the most potentially effective agent for Chagas chemoterapy.