Avaliação do potencial mutagênico e recombinogênico do cloridrato de bupropiona e do cloridrato de trazodona em células somáticas de Drosophila melanogaster

Abstract

According to the World Health Organization, around 7% of the Brazilian population is affected by psychic disorders related to depression. It is estimated that until 2020, depression will be the second most prevalent disease in the world. In light of this context, the use of antidepressants has increased exponentially. In order to evaluate the mutagenic and recombinogenic potential of the antidepressants: Bupropion Hydrochloride (CB) and Trazodone Hydrochloride (CT), the Somatic Mutation and Recombination Test (SMART) in wing cells of Drosophila melanogaster was used. Two crossings were realized: standard (ST) and high bioactivation (HB) cross . Third instar larvae (72 + 4h), obtained from both crosses, were treated with different concentrations 0.9375; 1.875; 3.75; 7.5 or 15 mg/mL. Ultrapure water and Urethane (10 mM) were used as negative and positive controls respectively. The highest concentration of BH and TH (15 mg/mL) was toxic. From the analysis of the trans-heterozygous descendants (MH), only the lowest concentration (0.9375 mg/mL) of the BH at the ST crossing did not increase the frequency of mutant spots significantly. The analysis of balancer heterozygous (BH) descendants indicated that genotoxic events induced by BH at ST crossing are mostly of recombinogenic origin. On the other hand, when they are metabolized by the enzyme complex of CYP450, they turn to be essentially mutagenic. All concentrations of TH increased the frequency of mutant spots significantly, regardless of crossover. After the analysis of the BH individuals, the three initial concentrations (0.9375, 1.875 and 3.75 mg/mL) were recombinogenic, both at ST and HB crossing. At the highest concentration (7.5 mg/mL) the genotoxic events were essentially mutagenic. Since the lack of data in the literature and the increased use of antidepressants by the world population, it is necessary further studies to elucidate the action mechanisms related to damage to genetic material caused by Bupropion Hydrochloride and Trazodone Hydrochloride.