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1.
PLoS One ; 12(4): e0174474, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28403142

RESUMO

Radiotherapy-induced gut toxicity is among the most prevalent dose-limiting toxicities following radiotherapy. Prevention of radiation enteropathy requires protection of the small intestine. However, despite the prevalence and burden of this pathology, there are currently no effective treatments for radiotherapy-induced gut toxicity, and this pathology remains unclear. The present study aimed to investigate the changes induced in the rat small intestine after external irradiation of the tongue, and to explore the potential radio-protective effects of melatonin gel. Male Wistar rats were subjected to irradiation of their tongues with an X-Ray YXLON Y.Tu 320-D03 irradiator, receiving a dose of 7.5 Gy/day for 5 days. For 21 days post-irradiation, rats were treated with 45 mg/day melatonin gel or vehicle, by local application into their mouths. Our results showed that mitochondrial oxidative stress, bioenergetic impairment, and subsequent NLRP3 inflammasome activation were involved in the development of radiotherapy-induced gut toxicity. Oral treatment with melatonin gel had a protective effect in the small intestine, which was associated with mitochondrial protection and, consequently, with a reduced inflammatory response, blunting the NF-κB/NLRP3 inflammasome signaling activation. Thus, rats treated with melatonin gel showed reduced intestinal apoptosis, relieving mucosal dysfunction and facilitating intestinal mucosa recovery. Our findings suggest that oral treatment with melatonin gel may be a potential preventive therapy for radiotherapy-induced gut toxicity in cancer patients.


Assuntos
Mucosa Intestinal/patologia , Intestino Delgado/patologia , Melatonina/administração & dosagem , Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/administração & dosagem , Animais , Apoptose , Avaliação Pré-Clínica de Medicamentos , Géis , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos da radiação , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/efeitos da radiação , Masculino , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fosforilação Oxidativa , Estresse Oxidativo , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Ratos Wistar , Língua/efeitos da radiação
2.
Neurodegener Dis ; 8(3): 109-16, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20714110

RESUMO

BACKGROUND/OBJECTIVE: Mitochondrial dysfunction, oxidative stress and protein metabolism impairment are the main molecular events underlying the pathogenesis of Parkinson's disease (PD). However, only few studies have addressed the changes produced by these phenomena in the blood of PD patients. Our purpose was to compare oxidative stress between newly diagnosed PD patients (ntPD) and PD patients under treatment (tPD). We also analyzed changes in plasma activity of several aminopeptidases (AP) involved in the metabolism of various active peptides. METHODS: Plasma lipid peroxide (LPO) and lactate (LAC) concentrations were measured by colorimetric methods, and plasma AP activities were determined by fluorometric assay. RESULTS: LPO and LAC concentrations were significantly elevated in ntPD and tPD patients versus controls, but there were no differences between the PD groups. Alanine-, cystine- and aspartate-AP activities were significantly lower in tPD versus ntPD patients. Nondenaturing electrophoresis and Western blot results confirmed these findings. CONCLUSIONS: The plasma LPO and LAC levels were high in both PD groups, indicating that they are elevated at an early stage of PD and are not affected by anti-PD treatment. The higher AP activities in ntPD versus tPD patients suggest that anti-PD treatment may improve protein metabolism while not altering oxidative stress. A therapy directed to reduce oxidative stress and normalize AP activity may be useful in the treatment of PD.


Assuntos
Aminopeptidases/sangue , Antiparkinsonianos/uso terapêutico , Estresse Oxidativo/fisiologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Idoso , Carbidopa/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Lactatos/sangue , Levodopa/uso terapêutico , Peróxidos Lipídicos/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/sangue
3.
Prog Neuropsychopharmacol Biol Psychiatry ; 31(5): 997-1005, 2007 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-17449160

RESUMO

OBJECTIVES: Some studies find a relationship between certain personality traits, as impulsivity or sensation seeking, and caffeine consumption, but these studies do not consider the potential confounding effect of smoking on caffeine intake, a co-occurrence that has been well demonstrated in epidemiological and clinical studies. The main objective of this cross-sectional study was to analyze the association of personality with caffeine intake controlling for the effects of smoking; a secondary objective was to explore the effect of caffeine intake on the previously known relationship between personality and smoking. METHODS: A sample of 498 adults answered a self-questionnaire including socio-demographic variables, and items regarding consumption of tobacco and caffeine. Personality was measured by the Temperament and Character Inventory (TCI-125). We analyzed the association of personality traits with both caffeine intake and smoking, controlling the possible confounding effects of sex, age and each substance with the other one. RESULTS: Logistic regression analyses showed that the temperamental dimension of novelty seeking was associated with heavy caffeine consumption (>200 mg/day) (adjusted OR=2.0; 95% CI: 1.1-3.9), controlling for the effect of smoking. Moreover, novelty seeking was associated with both smoking (adjusted OR=1.8; 95% CI: 1.1-2.9) and heavy smoking (>20 cigarettes/day) (adjusted OR=1.8; 95% CI: 1.0-3.7), after controlling for the effect of caffeine intake. CONCLUSION: Our study offers an epidemiological evidence of the relationship of novelty seeking, considered to be associated with low basal dopaminergic activity, with both nicotine consumption and heavy caffeine intake, two substances that enhance dopaminergic neurotransmission.


Assuntos
Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Personalidade/fisiologia , Fumar/psicologia , Adulto , Caráter , Estudos Transversais , Comportamento Exploratório/fisiologia , Feminino , Humanos , Comportamento Impulsivo/psicologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Motivação , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Testes de Personalidade , Fatores Socioeconômicos , Inquéritos e Questionários , Temperamento/fisiologia
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