INVESTIGADORES
LORES ARNAIZ Silvia
artículos
Título:
Nitric oxide, superoxide and hydrogen peroxide production in brain mitochondria after haloperidol treatment.
Autor/es:
LORES ARNAIZ, S.; CORONEL, M.F. ; BOVERIS, A.
Revista:
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
Editorial:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Referencias:
Año: 1999 vol. 3 p. 235 - 243
ISSN:
1089-8603
Resumen:
Inhibition of mitochondrial respiration and free radical induction have been suggested to be involved
in haloperidol neurotoxicity. In this study, mice were injected i.p. with haloperidol, according
to two different treatments: (a) a single injection (1 mg/kg), sacrificed 1 h after the injection (singledose
model); and (b) two injections (1 mg/kg each), sacrificed 24 h after the first dose (double-dose model).
Determinations of oxygen consumption and hydrogen peroxide (H2O2) production rate were carried
out in isolated brain mitochondria. Nitric oxide (NO) and superoxide (O2-) production rates were
measured in submitochondrial particles (SMP). Single-dose haloperidol treatment produced a 33%
inhibition in malateglutamate-dependent respiration, while no significant changes were found after
double-dose treatment. NO production was inhibited by 39 and 54% in SMP from haloperidol-treated
mice (single- and double-dose treatments, respectively) (control value: 1.6 6 0.2 nmol/min mg protein).
NO steady-state concentration was estimated at about 16.5 nM and was decreased by 40% by haloperidol
treatment. Increases of 105 and 54% were found in succinate-supported O2- and H2O2 production
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2- production rate when measured in the presence of NADH plus rotenone.
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
2-
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2- production rate when measured in the presence of NADH plus rotenone.
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
2-
2-
NO steady-state concentration was estimated at about 16.5 nM and was decreased by 40% by haloperidol
treatment. Increases of 105 and 54% were found in succinate-supported O2- and H2O2 production
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2- production rate when measured in the presence of NADH plus rotenone.
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
2-
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2- production rate when measured in the presence of NADH plus rotenone.
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
2-
2-
measured in submitochondrial particles (SMP). Single-dose haloperidol treatment produced a 33%
inhibition in malateglutamate-dependent respiration, while no significant changes were found after
double-dose treatment. NO production was inhibited by 39 and 54% in SMP from haloperidol-treated
mice (single- and double-dose treatments, respectively) (control value: 1.6 6 0.2 nmol/min mg protein).
NO steady-state concentration was estimated at about 16.5 nM and was decreased by 40% by haloperidol
treatment. Increases of 105 and 54% were found in succinate-supported O2- and H2O2 production
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2- production rate when measured in the presence of NADH plus rotenone.
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
2-
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2- production rate when measured in the presence of NADH plus rotenone.
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
2-
2-
NO steady-state concentration was estimated at about 16.5 nM and was decreased by 40% by haloperidol
treatment. Increases of 105 and 54% were found in succinate-supported O2- and H2O2 production
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2- production rate when measured in the presence of NADH plus rotenone.
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
2-
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2- production rate when measured in the presence of NADH plus rotenone.
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
2-
2-
out in isolated brain mitochondria. Nitric oxide (NO) and superoxide (O2-) production rates were
measured in submitochondrial particles (SMP). Single-dose haloperidol treatment produced a 33%
inhibition in malateglutamate-dependent respiration, while no significant changes were found after
double-dose treatment. NO production was inhibited by 39 and 54% in SMP from haloperidol-treated
mice (single- and double-dose treatments, respectively) (control value: 1.6 6 0.2 nmol/min mg protein).
NO steady-state concentration was estimated at about 16.5 nM and was decreased by 40% by haloperidol
treatment. Increases of 105 and 54% were found in succinate-supported O2- and H2O2 production
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2- production rate when measured in the presence of NADH plus rotenone.
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
2-
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2- production rate when measured in the presence of NADH plus rotenone.
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
2-
2-
NO steady-state concentration was estimated at about 16.5 nM and was decreased by 40% by haloperidol
treatment. Increases of 105 and 54% were found in succinate-supported O2- and H2O2 production
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2- production rate when measured in the presence of NADH plus rotenone.
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
2-
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2- production rate when measured in the presence of NADH plus rotenone.
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
2-
2-
measured in submitochondrial particles (SMP). Single-dose haloperidol treatment produced a 33%
inhibition in malateglutamate-dependent respiration, while no significant changes were found after
double-dose treatment. NO production was inhibited by 39 and 54% in SMP from haloperidol-treated
mice (single- and double-dose treatments, respectively) (control value: 1.6 6 0.2 nmol/min mg protein).
NO steady-state concentration was estimated at about 16.5 nM and was decreased by 40% by haloperidol
treatment. Increases of 105 and 54% were found in succinate-supported O2- and H2O2 production
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2- production rate when measured in the presence of NADH plus rotenone.
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
2-
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2- production rate when measured in the presence of NADH plus rotenone.
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
2-
2-
NO steady-state concentration was estimated at about 16.5 nM and was decreased by 40% by haloperidol
treatment. Increases of 105 and 54% were found in succinate-supported O2- and H2O2 production
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2- production rate when measured in the presence of NADH plus rotenone.
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
Our results suggest that haloperidol neurotoxicity would be mediated by a decreased mitochondrial
NO production, a decreased intramitochondrial NO steady-state concentration, and by an inhibition of
mitochondrial electron transfer with enhancement of O2- and H2O2 production. This inhibition does not
seem to be caused by increased NO or ONOO- formation.
seem to be caused by increased NO or ONOO- formation.
2-
2-
rates, respectively, after haloperidol single dose treatment. Haloperidol treatment generated a
248% increase in SMP O2-