Dados do Trabalho

Título

Carcinogenic Evaluation of Lisdexamfetamine Dimesylate through bioassay with Drosophila melanogaster

Resumo

Lisdexamfetamine Dimesylate is a psychotropic drug used as first-line therapy for Attention Deficit Hyperactivity Disorder. The lack of bio-safety studies on this compound demonstrates the need to verify long-term adverse effects. This study aimed to evaluate the carcinogenic effect of this amphetamine through the Epithelial Tumor Test (ETT) in Drosophila melanogaster. This test uses the interpretation of malignant phenotypes in the body segments of Drosophila, being used to study the mechanisms involved in tumor formation and the assessment of drug biosafety. ETT is used to assess the carcinogenic and anticarcinogenic effects of various chemical compounds since about 70% of cancer-causing genes have homologs in Drosophilas, including the wts gene homologous to human LATS1. In the present study, D. melanogaster larvae from the crossing of wts/TM3 and mwh/mwh mutant strains were treated with different concentrations of Lisdexamfetamine Dimesylate (0.125; 0,25; 0,5; 1.0 and 2.0 mM). Doxorubicin was used as a positive control, and for the negative control, ultrapure water was used. The results show a significant increase (p<0.05) in tumor frequencies in individuals treated with concentrations of 0,5; 1.0 and 2.0 mM of Lisdexamfetamine Dimesylate when compared to the negative control suggesting a dose-dependent carcinogenic effect in D. melanogaster. However, this assay contrasts with some previous studies for carcinogenic evaluation of the active ingredient d-amphetamine. Carcinogenicity studies indicated negative results upon continuous administration of this compound. Nonetheless, the authors cited various capacities of the active principle in indirectly inducing the formation of neoplasms. This is due to the substance's adverse effects, such as increased body temperature and anorexia, causing loss of adipose tissue, increasing the incidence of adenomas in the testicles, and myeloproliferative diseases. Therefore, it can be concluded that Lisdexamfetamine Dimesylate had a carcinogenic effect in vivo analysis model with D. melanogaster, but further investigations involving other biological models in vivo and in vitro are needed to verify drug safety in humans.

Palavras Chave

Lisdexamfetamine Dimesylate; Carcinogenic; Drosophila melanogaster