Avaliação da atividade de enzimas do sistema purinérgico e do perfil oxidativo em pacientes com adenocarcinoma colorretal esporádico

Abstract

Colorectal cancer (CRC) is a complex disease that is related to the disordered growth of colon and rectal cells, being related to hereditary, environmental and social conditions. According to estimates, incidence and mortality rates have increased worldwide, with the third most commonly diagnosed tumor in men and the second in women. Studies have revealed that alterations in purinergic signaling and oxidative events are closely associated with the development and progression of neoplasms, which is why the assessment of these aspects of cellular functions in a group of patients with sporadic CRC is extremely relevant. The aim of the present study was to evaluate the activity of the purinergic system enzymes - E-NTPDase, E-5'-nucleotidase and adenosine deaminase (ADA) - in platelets, as well as the serum oxidative profile, through the analysis of superoxide dismultase activity (SOD) and levels of total thiols (T-SH), non-protein thiols (NPSH), vitamin C (VIT C) and thiobarbituric acid reactive species (TBARS), in addition to myeloperoxidase (MPO) activity in a group of patients diagnosed with CRC of the histological subtype adenocarcinoma. For statistical analysis, data were first tested for normality, being subjected to statistical treatment using Student's t test. The significance level to be used is 0.05. The platelet, whole blood, serum and plasma samples used were collected by venipuncture (30 mL) from 30 patients diagnosed with CRC, prior to the beginning of surgical and/or pharmacological treatment of the tumor, with no family history of the disease; and healthy individuals of the same gender and similar age group. Patients who had any pathology other than sporadic CRC were excluded from the group of cases; and from the control group, those who had any type of disease. After the invitation and acceptance to participate in the study, the participants signed the Free and Informed Consent Term for participation in the study. From the analysis of the results, of the 30 individuals diagnosed with CRC, 63% (19 individuals) are men. Regarding the activity of E-NTPDase for the hydrolysis of ATP and ADP, a significant increase in the hydrolysis of nucleotides was observed in the group of patients with CRC when compared to the control group. Regarding E-5'-nucleotidase activity, an increase in AMP hydrolysis was also observed in the group of patients with CRC when compared to the control group. As for ADA activity, there was no significant difference between the groups studied by the analysis of the results. Furthermore, a decrease in MPO activity and an increase in SOD activity were observed, in addition to increased serum levels of NPSH, VIT C and TBARS in the group of sick individuals, when compared to the healthy control group. The results found demonstrate that the active tumor process promotes the release of ATP to the extracellular environment, increasing the activity of E-NTPDase. Excess ATP increases the pro-inflammatory process associated with neoplastic development and its hydrolysis into ADP by NTPDase contributes to the expansion of procoagulant effects commonly observed in patients with neoplastic diseases. Furthermore, patients with RCC had an increase in E-5'-nucleotidase activity and no change in ADA activity in platelets, suggesting that extracellular adenosine levels are elevated in them, providing advancement in tumor development in view of the tumor growth-promoting and angiogenesis-stimulating actions characteristic of adenosine. Regarding MPO, even though its activity is involved in inflammatory and carcinogenic processes, it seems to play a protective role in CRC. Its basal activity is related to the immune defense against tumors and its deficiency is linked to an increased incidence of colon tumors and chronic inflammation not linked to pathogens. Furthermore, the increase in hydrogen peroxide (H2O2), a substrate of MPO, is related to the progression of CRC. Furthermore, the increase in SOD activity in patients with CRC suggests the existence of a compensatory mechanism to the increase in the production of reactive oxygen species (ROS) in the tumor environment. Thus, the greater availability of substrate for this antioxidant enzyme would increase its activity. In addition, the increase in NPSH levels and the maintenance of T-SH levels within the normal range is strongly associated with the development of resistance of neoplastic cells to the antineoplastic therapeutic protocol. On the other hand, the increase in VIT C levels in patients with CRC makes evident the preventive action of this antioxidant on the deleterious actions of excess ROS in the circulation of cancer patients. For all these reasons, the results described here suggest that CRC exerts an important alteration in the activity of the enzymes of the purinergic system, as well as in the oxidative profile of patients, and these parameters may be useful in clinical medicine to monitor the pathology. It is hoped, therefore, that this work may contribute to a better understanding of the role of the purinergic system and the biomarkers of oxidative stress in the pathophysiology of CRC so that they become an important diagnostic and therapeutic tool.