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1.
Toxicol Appl Pharmacol ; 435: 115853, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973289

RESUMO

Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder. Although mounting studies have been conducted, no effective therapy is available to halt its progression. Indole-3-carbinol (I3C) is a naturally occurring compound obtained by ß-thioglucosidase-mediated autolysis of glucobrassicin in cruciferous vegetables. Besides its powerful antioxidant activity, I3C has shown neuroprotection against depression and chemically induced neurotoxicity via its anti-inflammatory and antiapoptotic effects. This study aimed to investigate the neuroprotective effects of I3C against rotenone (ROT)-induced PD in male albino rats. The possible protective mechanisms were also explored. PD was induced by subcutaneous administration of ROT (2 mg/kg) for 28 days. The effects of I3C (25, 50, and 100 mg/kg/day) were assessed by catalepsy test (bar test), spontaneous locomotor activity, rotarod test, weight change, tyrosine hydroxylase (TH) expression, α-synuclein (α-Syn) expression, striatal dopamine (DA) content, and histological examination. The highest dose of I3C (100 mg/kg) was the most effective to prevent ROT-mediated motor dysfunctions and amend striatal DA decrease, weight loss, neurodegeneration, TH expression reduction, and α-Syn expression increase in both the midbrain and striatum. Further mechanistic investigations revealed that the neuroprotective effects of I3C are partially attributed to its anti-inflammatory and antiapoptotic effects and the activation of the sirtuin 1/AMP-activated protein kinase pathway. Altogether, these results suggested that I3C could attenuate biochemical, molecular, and functional changes in a rat PD model with following repeated rotenone exposures.


Assuntos
Indóis/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/prevenção & controle , Rotenona , Sirtuína 1/metabolismo , Desacopladores , Animais , Peso Corporal/efeitos dos fármacos , Catalepsia/induzido quimicamente , Catalepsia/prevenção & controle , Dopamina/metabolismo , Masculino , Atividade Motora/efeitos dos fármacos , Neostriado/efeitos dos fármacos , Neostriado/metabolismo , Doença de Parkinson Secundária/psicologia , Equilíbrio Postural/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Sirtuína 1/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/metabolismo , alfa-Sinucleína/biossíntese , alfa-Sinucleína/efeitos dos fármacos
2.
Rheumatol Int ; 33(5): 1243-53, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23064543

RESUMO

This study was aimed to assess: (1) the additive diagnostic utility of diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA) over conventional MRI in detecting brain lesions in patients with acute primary neuropsychiatric systemic lupus erythematosus (NPSLE), and (2) the relevance of their findings to the associated NP manifestations. Included were 34 patients with acute NPSLE with mean age of 33.26 ± 10.14 years and duration of illness of 3.33 ± 1.71 years. Clinical interviewing and psychiatric and cognitive evaluations were performed by applying the criteria of the diagnostic and statistical manual of mental health disorders criteria (DSM-IV), Stanford Binet Subset Testing, Mini-Mental State Examination and Wechsler Memory Scale-Revised. Serologic tests included looking for antinuclear antibodies, anti-double strand DNA, anti-phospholipid antibodies. Radiologic evaluation included conventional MRI, DWI and MRA. One or more NP manifestations were diagnosed in 28 patients, in which cognitive deficits were reported with headache, psychosis and CVS. Anti-phospholipid antibodies were reported in patients with CVS. Twenty patients (71.43 %) with primary NPSLE (n = 28) had MRI abnormalities in which hyperintense signals at subcortical and periventricular white matter and at the junction between the gray and white matter represented 75 % (n = 15) and with headache (n = 6), psychosis (n = 6) and acute confusional state (n = 3) with and without cognitive deficits, respectively. Moderate-sized infarctions with restricted diffusion in the distribution of middle cerebral arteries were represented in 35 % (n = 7) and with CVS, of them, 71.43 % (n = 5) had beading and focal narrowing of carotid arteries were consistent with vasculitis. Brain atrophy represented 20 % (n = 4) and with psychosis. Compared to those with normal MRI, patients with MRI abnormalities were older (P < 0.050) and had longer duration of illness (P < 0.050). To conclude, although DWI and MRA are helping in more precise etiopathologic diagnosis compared to conventional MRI, but their relevance to the present NP manifestations is still limited.


Assuntos
Imagem de Difusão por Ressonância Magnética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Angiografia por Ressonância Magnética , Doença Aguda , Adolescente , Adulto , Anticorpos Antinucleares/sangue , Anticorpos Antifosfolipídeos/sangue , Atenção , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Cognição , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Masculino , Memória , Pessoa de Meia-Idade , Testes Neuropsicológicos , Valor Preditivo dos Testes , Prognóstico , Desempenho Psicomotor , Adulto Jovem
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