RESUMO
Lifestyle influences physical and cognitive development during the period of adolescence greatly. The most important of these lifestyle factors are diet and stress. Therefore, the aim of this study was to investigate the impact of high fat diet (HFD) and chronic mild stress on cognitive function and anxiety-like behaviors in young rats and to study the role of caffeic acid as a potential treatment for anxiety and cognitive dysfunction. Forty rats were assigned into 4 groups: control, HFD, HFD + stress, and caffeic acid-treated group. Rats were sacrificed after neurobehavioral testing. We detected memory impairment and anxiety-like behavior in rats which were more exaggerated in stressed rats. Alongside the behavioral changes, there were biochemical and histological changes. HFD and/or stress decreased hippocampal brain-derived neurotrophic factor (BDNF) levels and induced oxidative and inflammatory changes in the hippocampus. In addition, they suppressed Wnt/ß-catenin pathway which was associated with activation of glycogen synthase kinase 3ß (GSK3ß). HFD and stress increased arginase 1 and inducible nitric oxide synthase (iNOS) levels as well. These disturbances were found to be aggravated in stressed rats than HFD group. However, caffeic acid was able to reverse these deteriorations leading to memory improvement and ameliorating anxiety-like behavior. So, the current study highlights an important neuroprotective role for caffeic acid that may guard against induction of cognitive dysfunction and anxiety disorders in adolescents who are exposed to HFD and/or stress.
Assuntos
Ansiedade , Fator Neurotrófico Derivado do Encéfalo , Ácidos Cafeicos , Dieta Hiperlipídica , Glicogênio Sintase Quinase 3 beta , Hipocampo , Fármacos Neuroprotetores , Estresse Psicológico , Animais , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/uso terapêutico , Ratos , Glicogênio Sintase Quinase 3 beta/metabolismo , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Masculino , Dieta Hiperlipídica/efeitos adversos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ratos Wistar , beta Catenina/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Cognição/efeitos dos fármacos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Óxido Nítrico Sintase Tipo II/metabolismoRESUMO
Lung fibrosis is a critical interstitial lung disease with poor prognosis. There is an urgent need to develop a proper and cost-effective therapeutic modality that can reverse and/or ameliorate lung fibrosis. Vitamin E is one of the widely investigated dietary antioxidants which has been linked to improvement of many health problems. The current study was conducted to evaluate the possible roles of vitamin E in prevention and treatment of bleomycin (BLM) induced lung fibrosis. Physiological, anatomical, histopathological and immunohistochemical studies were done to assess and compare between the structure and function of the lung tissue in lung fibrosis model, early and late treated groups with vitamin E. Furthermore, measurement of transforming growth factor-ß(TGF-ß), E-cadherin, Smad-3, BAX, BCL2, malondialdehyde (MDA), and superoxide dismutase (SOD) were done. The study revealed that administration of vitamin E helped to improve signs of lung fibrosis, as reflected by amelioration of structure and functions of lungs as well as the decrease in TGF-ß levels and inhibition of α-SMA/collagen I profibrotic pathway. These findings highlight the importance of administration of vitamin E as a prophylactic agent prior to BLM therapy and as an adjuvant treatment in cases of lung fibrosis.