Avaliação do potencial mutagênico e recombinogênico do Pantoprazol® em células somáticas de Drosophila melanogaster

Abstract

Proton pump inhibitors (PPIs) have become a major asset in pharmacological armamentarium over the past 15 years. These drugs are substituted benzoimidazolics compounds, which resemble the H2 receptor antagonists in its structure, but have completely different mechanism of action. Pantoprazole® (Panto) is one of the most important PPI to treatment of a variety of diseases related to upper gastrintestinal tract. Studies have shown an increased risk for developing gastric cancer, intestinal metaplasia and hyperplasia of endocrine cells after prolonged use of H+ K+/ATPase inhibitors. In this work, the Somatic Mutation And Recombination Test in Drosophila melanogaster (SMART) was employed to determine the mutagenic effects of Panto. Chronic treatments with Panto were performed with 72 hours old larvae of the standard (ST) cross and high bioactivation cross (HB) at concentrations of 2,5; 5,0; or 10,0 μM. In addition, the chemoterapeutic doxorrubicin (DXR) was administered at 0,4 mM, as a positive control. When administered in isolation at ST cross total spots was only statistically relevant in 2.5 and 5.0 μ M concentrations and when associated with DXR, the frequency of small spots was reduced. When analyzing the mutagenicity at HB cross, found a significant increase in the total number of spots of descendants MH, so proceed the analysis of BH descendants, found recombinogenic effect at all concentrations. On the other hand, when evaluate the association found significant increase in frequency of twin spots only. Faced with such experimental conditions and results, we can say that the Pantoprazole is a direct genotoxic and has DXR enhancer effect, these results reveal that the Pantoprazole is recombinogenic and enhancer of the DXR recombinogenic effects.