ABSTRACT
Parkinson's disease (PD) induced by environmental toxins involves a multifactorial cascade of harmful factors, thus motivating the search for therapeutic agents able to act on the greatest number of molecular targets. This study evaluated the efficacy of 50 mg/kg purified anacardic acids (AAs), isolated from cashew nut shell liquid, on multiple steps of oxidative stress and inflammation induced by rotenone in the substantia nigra (SN) and striatum. Adult mice were divided into four groups: Control, rotenone, AAs + rotenone, and AAs alone. Lipoperoxidation, nitric oxide (NO) levels, and reduced glutathione (GSH)/oxidized gluthatione (GSSG) ratio were evaluated. NF-kB-p65, pro-IL-1ß, cleaved IL-1ß, metalloproteinase-9, Tissue Inhibitory Factor-1 (TIMP-1), tyrosine hydroxylase (TH), and glial fibrillary acidic protein (GFAP) levels were assessed by Western blot. In silico studies were also made using the SwissADME web tool. Rotenone increased lipoperoxidation and NO production and reduced TH levels and GSH/GSSG ratio in both SN and striatum. It also enhanced NF-kB-p65, pro, and cleaved IL-1ß, MMP-9, GFAP levels compared to control and AAs groups. The AAs alone reduced pro-IL-1ß in the striatum while they augmented TIMP1 and reduced MMP-9 amounts in both regions. AAs reversed rotenone-induced effects on lipoperoxidation, NO production, and GSH/GSSG ratio, as well as increased TH and attenuated pro-IL-1ß and MMP-9 levels in both regions, NF-kB-p65 in the SN and GFAP in the striatum. Altogether, the in vivo and in silico analysis reinforced multiple and defined molecular targets of AAs, identifying that they are promising neuroprotective drug candidates for PD, acting against oxidative and inflammatory conditions induced by rotenone.
Subject(s)
Anacardic Acids/pharmacology , Neuroprotective Agents/pharmacology , Parkinson Disease, Secondary/drug therapy , Parkinson Disease/drug therapy , Pesticides/toxicity , Anacardic Acids/chemistry , Anacardic Acids/isolation & purification , Animals , Computer Simulation , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Corpus Striatum/pathology , Glial Fibrillary Acidic Protein/genetics , Glutathione/metabolism , Glutathione Disulfide/metabolism , Humans , Interleukin-1beta/genetics , Lipid Peroxidation/drug effects , Matrix Metalloproteinase 9/genetics , Mice , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Parkinson Disease/etiology , Parkinson Disease/genetics , Parkinson Disease/pathology , Parkinson Disease, Secondary/chemically induced , Parkinson Disease, Secondary/genetics , Parkinson Disease, Secondary/pathology , Tissue Inhibitor of Metalloproteinase-1/genetics , Transcription Factor RelA/genetics , Tyrosine 3-Monooxygenase/geneticsABSTRACT
Objetivo: Avaliar a severidade de inflamação gengival perante duas condições, estresse e gravidez, em um grupo de adolescentes atendidas no serviço público de saúde na cidade de Maceió-AL. Material e métodos: 80 adolescentes grávidas com faixa etária ente 14 e 19 anos, atendidas em centros de referência ao atendimento pré-natal na cidade de Maceió-AL, participaram desse estudo piloto. O estresse social foi avaliado subjetivamente pelo teste de avaliação de estresse e a inflamação gengival foi avaliada pelo índice de inflamação gengival através de um exame clínico utilizando-se 6 dentes índices. A análise estatística foi executada relacionando o estresse social com dados demográficos e de hábitos de higiene oral e com relação a inflamação gengival pelo teste de Mann-Whitney e pelo teste de Fischer para variáveis dicotômicas. Resultados: Na avaliação da relação do estresse com a inflamação gengival e com o índice de placa com controle das variáveis independentes foi utilizada a regressão logística multivariada. Todos os testes foram aplicados com nível de confiança de 95%. O teste de Mann-Whitney demonstrou que as grávidas estressadas apresentavam maior frequência de escovação que as grávidas sem stress (p=0.008). Os outros dados demográficos e de hábitos de higiene oral se distribuíram igualmente entre os grupos. A análise por regressão logística multivariada demonstrou que nenhuma das variáveis independentes influenciou no índice gengival e no índice de placa em mulheres grávidas com ou sem stress. Conclusão: O estresse não causou aumento da severidade da inflamação gengival em adolescentes grávidas.
Objective: Evaluate the severity of gingival inflammation against two conditions, stress and pregnancy, in a group of adolescents treated at a public health service in Maceió-AL. Material and methods: 80 pregnant adolescents aged between 14 to 19 years being treated at referral centers for prenatal care in the city of Maceió-AL, participated in this pilot study. The social stress was subjectively evaluated by assessment of stress test (Lipp test) and gingival inflammation was assessed by the index of gingival inflammation (Loe & Silness) through a clinical examination using six index teeth. Statistical analysis was performed relating the social stress with demographic data and habits regarding oral hygiene and gingival inflammation using the Mann-Whitney and Fischer's test for dichotomous variables. Results: When considering the influence of the stress in gingival inflammation and plaque index with controlled of theindependent variables the multivariate logistic regression was used. All tests were applied with a confidence level of 95%. The Mann-Whitney test demonstrated that pregnant women under stress showed higher frequency of brushing than pregnant women without stress (p = 0.008). The other demographic and oral hygiene habits were equally distributed between the groups. A multivariate logistic regression analysis showed that none of the independent variables influenced the gingival index and plaque index in pregnant women with or without stress. Conclusion:The stress did not increase the severity of gingival inflammation in pregnant adolescents.
