RESUMO
No-caloric sweeteners, such as aspartame, are widely used in various food and beverages to prevent the increasing rates of obesity and diabetes mellitus, acting as tools in helping control caloric intake. Aspartame is metabolized to phenylalanine, aspartic acid, and methanol. Our aim was to study the effect of chronic administration of aspartame on glutathione redox status and on the trans-sulphuration pathway in mouse liver. Mice were divided into three groups: control; treated daily with aspartame for 90 days; and treated with aspartame plus N-acetylcysteine (NAC). Chronic administration of aspartame increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase activities and caused liver injury as well as marked decreased hepatic levels of reduced glutathione (GSH), oxidized glutathione (GSSG), γ-glutamylcysteine ââ(γ-GC), and most metabolites of the trans-sulphuration pathway, such as cysteine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine ââ(SAH). Aspartame also triggered a decrease in mRNA and protein levels of the catalytic subunit of glutamate cysteine ligase (GCLc) and cystathionine γ-lyase, and in protein levels of methionine adenosyltransferase 1A and 2A. N-acetylcysteine prevented the aspartame-induced liver injury and the increase in plasma ALT activity as well as the decrease in GSH, γ-GC, cysteine, SAM and SAH levels and GCLc protein levels. In conclusion, chronic administration of aspartame caused marked hepatic GSH depletion, which should be ascribed to GCLc down-regulation and decreased cysteine levels. Aspartame triggered blockade of the trans-sulphuration pathway at two steps, cystathionine γ-lyase and methionine adenosyltransferases. NAC restored glutathione levels as well as the impairment of the trans-sulphuration pathway.
Assuntos
Aspartame/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Glutationa/metabolismo , Edulcorantes/efeitos adversos , Acetilcisteína/administração & dosagem , Animais , Aspartame/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/patologia , Cistationina gama-Liase/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glutamato-Cisteína Ligase/genética , Humanos , Fígado/metabolismo , Fígado/patologia , Metionina Adenosiltransferase/genética , Camundongos , Edulcorantes/administração & dosagemRESUMO
No contexto das doencas neoplasicas, o cancer do intestino grosso do homem e da mulher e o terceiro em incidencia e o segundo em mortalidade. Apesar de sua existencia ja descrita na antiguidade e dos progressos no seu diagnostico, bem como do arsenal terapeutico disponivel, os resultados sao ainda desapontadores com relacao ao indice de sobrevida, porem estimulantes quanto a qualidade de vida proporcionados pelo desenvolvimento de novas tecnicas. Devido a estes fatos, os autores abordam o tema dando destaque a aspectos historicos, os diagnosticos e a terapeutica
