RESUMO
BACKGROUND: Aprotinin has been used in cardiosurgery as a hemostatic agent. Considering the implication of oxygen reactive species and proteases in the pathogenesis of Systemic Inflammatory Response Syndrome, we hypothesized that aprotinin may exert an antioxidant effect. This work was designed to evaluate the antioxidant capacity of aprotinin in vitro and in vivo in child patients undergoing cardiosurgery with mechanical cardiorespiratory support. METHODS: Colorimetric techniques and chemiluminiscent emission assays. A blind controlled clinical trial was performed with a control (G-1, n=14, without aprotinin) and treated with aprotinin (G-2, n=12) groups (both assessed by medical decision) of child patients undergoing cardiosurgery with mechanical cardiorespiratory support. Blood samples were taken at: T-0 (induction of anesthesia), T-1 (10 minutes after begining of perfusion), T-2 (5 minutes after anoxic heart arrest), T-3 (ending operation) and T-4 (24 hours after operation). RESULTS: We proved that aprotinin has no hydroxyl radical, superoxide anion nor H2O2 scavenger capacity as well as its capacity for inhibiting in vitro activated-leukocyte chemiluminiscence. Malonildialdehyde levels were higher in G-1 than G-2 with the greatest difference at T-2 (7.2+/-3.6 nmol/ml in G-1 vs 4+/-1.65 in G-2). Phospholipase A2 activity showed a tendency of higher values in G-1 than G-2 although there was no statistical significance. Uric acid concentration was greater in G-2 at T-1, T-2, T-3 and T-4 than G-1 and catalase activity was higher in G-2 at T-0, T-2 and T-3 than G-1 with noteworthy difference only at 5 minutes after anoxic heart arrest. Low cardiac output, arrhythmias and sudden death in the early postoperative phase were less frequent in the treated group. CONCLUSIONS: These results suggest that aprotinin exerts a primary antioxidant activity and its protective effects in cardiosurgery seem to be associated with reduction of systemic oxidative stress.
Assuntos
Antioxidantes/uso terapêutico , Aprotinina/uso terapêutico , Procedimentos Cirúrgicos Cardíacos , Respiração Artificial , Catalase/metabolismo , Criança , Pré-Escolar , Colorimetria , Circulação Extracorpórea , Humanos , Técnicas In Vitro , Medições Luminescentes , Estresse Oxidativo/efeitos dos fármacos , Fosfolipases A/metabolismo , Fosfolipases A2 , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Ácido Úrico/metabolismoRESUMO
INTRODUCTION AND OBJECTIVE: Parkinson's disease (PD) is characterized by a progressive, slow loss of dopaminergic neurones in the substance nigra. Although the cause of this neurone loss is unknown, at the present time many papers suggest oxidative stress (OS), secondary to dopaminergic metabolism, as an aetiopathogenic factor of PD. Therefore study of the part played by OS in this would permit the use of antioxidants (AO) as another possibility for treatment of the disease. It would also be a major step forward in the search for possible biological markers. MATERIAL AND METHODS: A study using spectrophotometric techniques was made of the serum levels of four biochemical indicators: catalase (CAT), malonyl aldehyde (MDA), phospholipase A2 (PLA2) and Vitamin C (VITC) in controls and in patients with PD. We found the average value for each of the variables studied in controls and in patients, taking AO treatment into account. RESULTS: The effect of clinical variables on serum levels of CAT, MDA, PLA2 and VITC was analyzed. It was seen that only the clinical state of Hoen and Yahr was related to the biochemical indicators. The CAT activity and VITC concentration showed statistically significant differences between patients (independently of their AO treatment) and controls. The CAT activity was significantly less in those treated with AO. The patients with PD did not all have the same degree of OS. The effect of AO treatment on plasma markers showed changes only in one subgroup of Parkinson patients. CONCLUSIONS: Our study suggests that AO treatment in this condition should be tailored to the individual patient according to the degree of OS present.
Assuntos
Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Ácido Ascórbico/sangue , Biomarcadores , Catalase/sangue , Progressão da Doença , Humanos , Malondialdeído/sangue , Doença de Parkinson/enzimologia , Fosfolipases A/sangue , Fosfolipases A/metabolismo , Fosfolipases A2 , Espécies Reativas de Oxigênio/metabolismo , Espectrofotometria/métodosRESUMO
Introducción y objetivo. La enfermedad de Parkinson (EP) se caracteriza por una pérdida lenta y progresiva de las neuronas dopaminérgicas localizadas en la sustancia nigra. Aunque no se conoce la causa de la pérdida neuronal, en la actualidad es frecuente encontrar trabajos que proponen el estrés oxidativo (EO), secundario al metabolismo dopaminérgico, como factor etiopatogénico en la EP; por tanto, profundizar en el conocimiento del papel que desempeña el EO en ésta permitirá utilizar los antioxidantes (AO) como una alternativa más en el tratamiento de la enfermedad, además de constituir un paso importante en la búsqueda de posibles marcadores biológicos. Material y métodos. Se realizó un estudio de los niveles séricos de cuatro indicadores bioquímicos: catalasa (CAT), malonilaldehido (MDA), fosfolipasa A2 (PLA2) y vitamina C (VITC) en controles y pacientes con EP mediante técnicas espectrofotométricas. Se determinó la media para cada una de las variables estudiadas en controles y pacientes tomando en consideración el tratamiento AO. Resultados. Se analizó la influencia de las variables clínicas sobre los niveles séricos de la CAT, MDA, PLA2 y VITC y se observó que sólo el estadio clínico de Hoen y Yahr estaba relacionado con los indicadores bioquímicos. La actividad de la CAT y la concentración de VITC presentaron diferencias estadísticamente significativas entre pacientes (independientemente del tratamiento AO) y controles, siendo la actividad CAT significativamente menor en los tratados con AO. Todos los pacientes con EP no presentaron el mismo grado de EO; la influencia del tratamiento AO sobre los indicadores séricos sólo mostró diferencias en un subgrupo de parkinsonianos. Conclusiones. Nuestro estudio sugiere que el tratamiento AO en esta enfermedad debe ser individualizado y en concordancia con el grado de EO que presente el paciente