Investigação da toxicidade genética de produtos naturais através de bioensaios de curta duração

Abstract

Natural products derived from plants are used as raw material for the synthesis of phytotherapeutics, and are widely used by many populations around the world. Among these compounds, there are the saponins and its metabolites. Its intense use is due to its bioactive properties, added to its structural similarity to hormones. Saponins derived in sapogenins, as Diosgenin and Hecogenin. Besides its use by pharmaceutical industries to synthesis of steroidal hormones and anti-inflammatories, these two sapogenins are also used as phytotherapeutics, being also present in vegetables from diets of many populations. Despite the widespread use of these compounds, there are a lack of information about their genetic toxicity, which makes the use of these sapogenins a risk. Given this context, the present work aimed to investigate the toxic potential of Diosgenin and Hecogenin, at cellular and DNA level. Assays with HepG2 cells was performed to evaluate the cytotoxicity, genotoxicity and mutagenicity. Considering the results obtained with Diosgenin, that sapogenin showed cytotoxic effects at concentrations higher than 30 M, as well as significantly induced increases in frequency of DNA damage and micronucleus. On the other hand, Hecogenin only revealed cytotoxicity above 150 M, however, at concentrations below this value, it was able to induce DNA damage without promote an increase in micronucleus frequency. The analysis of these results together suggests that the consumption of foods, phyotheraputics or medicines containing Diosgenin on its composition, presents a higher risk of toxicity when compared with formulations with Hecogenin, since Diosgenin shows a mutagenic potential demonstrated by a significant increase in micronucleus frequency, which are biomarkers of genome instability.