Avaliação preliminar da associação entre anfotericina e hesperina com oxidantes e células huvec

A anfotericina B (AmB) e farmaco “padrao ouro” para o tratamento de infeccoes fungicas invasivas desde 1960. Entretanto, a anfotericina B apresenta elevada toxicidade, a qual manifesta-se mais frequentemente nos rins e no figado. Sabe-se, desde 1985, que a auto-oxidacao da AmB origina diferentes formas de especies reativas oxidativas e estas, por serem toxicas para a celula, seriam responsaveis, em parte, pela toxicidade. Diferentes estudos indicam que a hesperidina contribui por meio do decrescimo do estresse oxidativo, para a protecao renal e contra a injuria gerada pela isquemia. Tal fato e o envolvimento da AmB na geracao de radicais livres tornam interessante a avaliacao preliminar do efeito da hesperidina e AmB (isoladamente ou associadas) frente a especies reativas do oxigenio e radicais livres, bem como o estudo das mesmas em modelos de citoxicidade. Frente ao ABTS•+, a AmB apresentou IC50 igual a 0,0124mg/mL, mas quando associada a hesperidina este valor caiu para 0,0003mg/mL. Frente ao HOCl, a Amb apresentou IC50 igual a 0,0056, mas quando associada a hesperidina este valor caiu para 0,0023mg/mL. No ensaio com DPPH• e radical ânion superoxido as amostras nao foram efetivas. No ensaio com celulas endoteliais em cultivo (HUVEC), as associacoes reduziram a viabilidade celular. Estes resultados preliminares evidenciam a interacao dos compostos com especies reativas bem como indicam possibilidade de exacerbacao do dano pela AmB na presenca dos antioxidantes em um modelo in vitro. Palavras-chave: Hesperidina. Anfotericina B. Estresse oxidativo. Citotoxicidade. ABSTRACT Preliminary assessment of the association between amphotericin and hesperetin with oxididants and huvec cells Amphotericin B (AmB) is drug “gold standard” for the treatment of invasive fungal infections since 1960. However, amphotericin B has high toxicity, which manifests itself most often in the kidneys and in the liver. It is known, since 1985, that self-oxidation of AmB gives different forms of reactive oxidative species and these, being toxic to the cell, would be responsible, in part, by its toxicity. Different studies indicate that hesperidin contributes, through the reduction of oxidative stress, to protect against renal injury generated by ischemia. This fact and the involvement of AmB in the generation of free radicals make it interesting the preliminary evaluation of the effect of hesperidin and AmB (alone or associated) against reactive oxygen species and free radicals, as well as the study on models of cytotoxicity. Front ABTS•+, AmB presented IC50 equal to 0.0124 mg/mL, but when it was associated to hesperidin this value has decreased to 0.0003 mg/mL. Front HOCl, Amb presented IC50 equal to 0.0056, but when it was associated to hesperidin this value has decreased to 0.0023 mg/mL. In the trials with DPPH• and the superoxide anion radical samples were not effective. In the assay with endotelial cell culture (HUVEC cells), the association has decreased cell viability. These preliminary results demonstrate the interaction of the compounds with reactive species as well as indicate the possibility of damage exacerbation by AmB in the presence of antioxidants in an in vitro model. Keywords: Hesperidin. Amphotericin B. Oxidative stress. Cytotoxicity.