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1.
Brain Res ; 1515: 1-11, 2013 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-23566814

RESUMO

Cerebellar atrophy during ageing can produce neurobehavioural changes characterized by cognitive and motor impairment. Chronic exposure to D-galactose, a reducing sugar can accelerate ageing by producing an unprecedented rise in oxidative load. This can enhance neuronal damage by promoting the oxidation of protein and lipids. We perceived that the simultaneous administration of piperine and curcumin, two powerful antioxidants can exert neuroprotective effect by inhibiting damage caused by the chronic exposure to D-galactose. Young Wistar rats treated with D-galactose (150 mg/kg, s.c.) were simultaneously treated with piperine alone, curcumin separately; and in combination for a period of 56 days by the oral route. A vehicle control, D-galactose alone and naturally aged control were also evaluated. Cognitive changes, motor impairment, protein carbonyls, protein thiols, advanced oxidation protein products, 4 hydroxynonenol and nitric oxide levels were determined in the brain homogenate. In order to ascertain the impact of cerebellum on motor performance, histopathological changes in the cerebellum were also established. Results obtained from our studies reflect a marked improvement in memory, sensorimotor performance, reduced oxidative and nitrosative burden on simultaneous treatment with piperine and curcumin. Furthermore, alterations produced in the Purkinje cells were minimized on treatment with the combination. Our studies demonstrated the influence of protein and lipid oxidation products on behavioural changes in D-galactose induced ageing model. Incorporation of these antioxidants might reduce the risk of developing neurodegenerative disorders, an important counterpart of advancing age.


Assuntos
Envelhecimento/metabolismo , Alcaloides/administração & dosagem , Benzodioxóis/administração & dosagem , Encéfalo/metabolismo , Curcumina/administração & dosagem , Galactose/toxicidade , Peroxidação de Lipídeos/fisiologia , Estresse Oxidativo/fisiologia , Piperidinas/administração & dosagem , Alcamidas Poli-Insaturadas/administração & dosagem , Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Animais , Antioxidantes/administração & dosagem , Encéfalo/efeitos dos fármacos , Combinação de Medicamentos , Galactose/antagonistas & inibidores , Peroxidação de Lipídeos/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar
2.
Eur J Pharmacol ; 703(1-3): 91-9, 2013 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-23200897

RESUMO

Aging is associated with progressive decline in mental abilities and functional capacities. Postmitotic tissues are most vulnerable to alteration due to oxidative damage leading to behavioral and biochemical changes. We hypothesized that the anatomical and functional facets of the brain could be protected with powerful antioxidants such as piperine and curcumin by examining their effects individually and in combination in delaying senescence induced by d-galactose. Young adult male Wistar rats were treated with piperine (12 mg/kg) alone, and curcumin (40 mg/kg) alone; and in combination for a period of 49 days by the oral route with treatment being initiated a week prior to d-galactose (60 mg/kg, i.p.). A control group, d-galactose alone and naturally aged control were also evaluated. Behavioral tests, hippocampal volume, CA1 neuron number, oxidative parameters, formation of lipofuscin like autofluorescent substances, neurochemical estimation, and histopathological changes in CA1 region of hippocampus were established. Our results suggest that the combination exerted a superior response compared to monotherapy as evidenced by improved spatial memory, reduced oxidative burden, reduced accumulation of lipofuscin; improvement in signaling, increase in hippocampal volume and protection of hippocampal neurons. We speculate that the powerful antioxidant nature of both, augmented response of curcumin in the presence of piperine and enhanced serotoninergic signaling was responsible for improved cognition and prevention in senescence.


Assuntos
Envelhecimento/efeitos dos fármacos , Alcaloides/administração & dosagem , Antioxidantes/administração & dosagem , Benzodioxóis/administração & dosagem , Encéfalo/efeitos dos fármacos , Curcumina/administração & dosagem , Piperidinas/administração & dosagem , Alcamidas Poli-Insaturadas/administração & dosagem , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Catalase/metabolismo , Sinergismo Farmacológico , Galactose , Glutationa/metabolismo , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Células Piramidais/efeitos dos fármacos , Células Piramidais/patologia , Ratos , Ratos Wistar , Serotonina/metabolismo , Superóxido Dismutase/metabolismo
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