Avaliação da atividade das enzimas do sistema purinérgico em plaquetas de pacientes com lesão intraepitelial de alto grau do colo uterino

Abstract

High grade cervical intraepithelial lesions (HSIL) are precursors of uterine cervical cancer (CCU), occurring especially associated to oncogenic subtypes of Human Papillomavirus (HPV). For a long time it has been proposed that modifications in the purinergic signaling are associated with the occurrence of countless pathological processes, including HSIL and CCU. Are part of the purinergic system, specially, the adenine nucleotides and the nucleoside adenosine, which act in purinereceptors and are metabolized by enzymes such as NTDPase (CD39), 5’-nucleotidase (CD73) and adenosine deaminase (ADA), and are present in countless celular types, including malignant cells, and also in platelets. By the existence of some evidence that links the development and progression of cervical lesions to modifications in the purinergic enzymes activity, it becomes fundamental to clarify the mechanisms involved in the pathophysiology of these processes. Thus, the present study aimed to evaluate the activity of CD39, CD73 and ADA in platelets of women diagnosed with HSIL, before any therapeutic intervention, compared to a healthy control group. Were part of this study 32 women with cytopathological diagnosis of HSIL and 40 women from the control group. The enzymatic activities were evaluated by colorimetric method and the results were expressed as mean ± standard deviation, with p<0,05 being considered statistically significant. As for results, women with HSIL presented higher activity of CD39 and CD73 and a lower activity of ADA when compared to the healthy control group. These results suggest that nucleotides ATP, ADP and AMP are being extensively hydrolyzed in patients with cervical lesions, promoting an accumulation of adenosine in the organism. Taken together, our findings corroborate to an understanding that the increase in adenosine levels favors an immunosuppressed state, through production of IL-10 and TGF-β1, which would favor the progression of the cervical intraepithelial lesion, as well as, facilitate the development of invasive tumors.