Câncer de tireoide: avaliação da atividade de enzimas do sistema purinérgico, butirilcolinesterase e perfil oxidativo

Abstract

Thyroid cancer is the most common endocrine neoplasia, and its incidence has been increasing in recent years. A better understanding of the molecular events involved in the progression of thyroid cancer may aid in the identification of patients with low and high-risk carcinomas. Among the mediators capable of modulating immune processes, such as cell differentiation, we highlight ATP, ADP, AMP, and adenosine, whose extracellular concentrations are controlled by the activity of the ectonucleoside triphosphate 5'-diphosphohydrolase (E- NTPDase), E-5'-nucleotidase (E-5’-NT) ectoenzymes and adenosine deaminase (ADA), and which act on specific receptors, forming the purinergic system. It is well known the relationship between reactive oxygen species (ROS) and cancer, in which ROS can contribute to the neoplastic transformation of cells. ROS are normally produced by metabolic oxidative processes and the molecules often damaged by them are lipids, proteins, and DNA. Antioxidant defense systems work cooperatively to relieve oxidative stress caused by increased production of ROS. Any change in one of these systems can break that balance and cause cell damage and, ultimately, malignant transformation. In addition, butyrylcholinesterase (BChE) appears to play important non-cholinergic roles as it is capable of intervening in cellular processes such as proliferation, differentiation, and apoptosis, suggesting a possible influence on tumorigenesis. The objective of this work is a better understanding of the molecular processes that occur during the progression of thyroid cancer, in order to identify possible new therapeutic targets. Therefore, we investigated the purinergic signaling profile in patients with thyroid cancer through platelet determination of E-NTPDase and E-5’-NT enzyme activities, as well as platelet and serum determination of ADA activity, by spectrophotometry. We also investigated the oxidative profile, through the determination of ROS levels and the biological damage caused by reactive species in lipids and proteins by the determination of lipid peroxidation and carbonylation levels of proteins. In addition, we verified the antioxidant profile of thyroid cancer patients by determining the levels of total thiols (T-SHs) and reduced glutathione (GSH). The serum activity of BChE was also performed. We observed a significant reduction in E-NTPDase activity, both in ATP and ADP hydrolysis. These results suggest an increase in ATP concentration as a consequence of a self-protection mechanism, and ADP, favoring thromboembolic changes. However, a significant increase in E-5’-NT activity has been observed, which, together with the reduction of ADA activity in both platelets and serum, leads to an increase in the extracellular concentration of adenosine, which may be involved in the tumor progression. Analyzing the oxidative profile, we observed a significant increase in the levels of ROS, which, together with the absence of a concomitant increase in antioxidant defenses represented by T-SHs and GSH levels, generate a pro-oxidant environment that justifies the elevated levels of thiobarbituric acid reactives substances (TBARS). The significant increase in BChE activity may be related to the stage of tumor progression, since patients in the study had pronounced nodules indicating a more advanced stage of cancer. The results demonstrated that, during the progression of thyroid cancer, alterations occur both in the activity of the enzymes of the purinergic and cholinergic systems as well as in the oxidative profile of these patients. Therefore, such parameters may represent future targets for the therapy and monitoring of the evolution of this neoplasm.