ABSTRACT
Abstract Four bisabolanes 1–4, including perezone (1) and triacetyl perezone (2), were isolated through a bioassay-guided fractionation of the extract obtained from the Caribbean gorgonian coral Pseudopterogorgia rigida collected during an expedition cruise to the Bahamas. All isolated compounds showed to be cytotoxic toward panel of four human tumor cell lines, as quantified by the MTT assay after 72 h incubation. Perezone (1), the most active one, was further analyzed, showing to be cytotoxic, but not selective, in a 12-cell line panel comprising tumor and non-tumor, as well as human and murine cells. Additionally, 1 was assayed for cytotoxicity against HL-60 leukemic cells. Pre-treatment with an acute free radical scavenger (L-NAC) before exposure of cells to perezone virtually eliminated the generation of intracellular ROS and lessened its severe cytotoxicity. The protective effect delivered by L-NAC evidences that the mechanism of perezone-induced cytotoxicity is partially associated to production of ROS and a consequent induction of oxidative stress.
ABSTRACT
OBJETIVO: Revisar a estrutura e o funcionamento do sistema colinérgico central ressaltando seu papel na fisiologia e na fisiopatologia das doenças de Alzheimer e Parkinson, esquizofrenia, epilepsia e tabagismo. MÉTODO: Foi realizada uma pesquisa bibliográfica no MedLine, LILACS, PubMed e ISI, e na Biblioteca da Fundação Oswaldo Cruz, RJ, selecionando-se o período de 1914 a 2009, utilizando os descritores: "receptors", "cholinergic", "Alzheimer disease", "schizophrenia", "epilepsy" e "smoking", além de referências cruzadas dos artigos selecionados e análise adicional de referências na literatura específica do tema. RESULTADOS: Efeitos importantes da ativação de receptores colinérgicos nicotínicos e muscarínicos sobre o desenvolvimento do sistema nervoso central (SNC) têm sido descritos. A dessensibilização e a internalização dos receptores acoplados à proteína G mediadas pela ativação de proteínas cinases têm sido descritas em proliferação, diferenciação e morte celular, além de síndromes neuropsiquiátricas. CONCLUSÃO: As informações produzidas a partir de estudos do sistema de neurotransmissão colinérgica podem auxiliar no desenvolvimento de medicamentos mais específicos para o tratamento da doença de Alzheimer, esquizofrenia, epilepsia e tabagismo.
OBJECTIVES: To review articles regarding important topics about cholinergic system and its ionotropic and G-protein coupled receptors as well as their regulation, also enlightening its importance in central nervous system (CNS) development and in several neuropsychiatric conditions such as Alzheimer disease, schizophrenia, epilepsy and smoking. METHOD: Bibliographical research was completed through MedLine, LILACS, PubMed, ISI and the Fundação Oswaldo Cruz Library, RJ, specifically for 1914 to 2009, using the descritors: "receptors", "cholinergic", Alzheimer "disease", "schizophrenia", "epilepsy" and "smoking", in addition to the cross-reference of the articles selected and further analyses of bibliographical references on the theme. RESULTS: Currently literature describes important effects of nicotinic and muscarinic receptors activation on development of central nervous system (CNS). The protein G coupled receptors dessensibilization and internalization mediated by kinases have been described in proliferation, differentiation and cell death, and also in neurologic disorders. DISCUSSION: The importance of the cholinergic system and its relationship with pathologies such as Alzheimer disease, schizophrenia, epilepsy is evident. The data produced so far may help on planning medicaments more specific for these pathologies treatment.