"O papel da via NRF2-ARE na adaptação redox celular durante crises vaso-oclusivas em pessoas com anemia falciforme. "

Abstract

Sickle cell anemia (SCA) is a disease that presents wide clinical heterogeneity. Studies aimed at identifying genetic and biochemical modulators have contributed to the understanding of the pathophysiological mechanisms of the disease. Among these mechanisms, chronic oxidative stress, resulting from the failure of antioxidant defense systems, plays a central role in the cellular damage observed. In this context, the NRF2-ARE pathway plays a fundamental role in regulating the expression of antioxidant genes essential for maintaining redox balance in the erythrocytic environment. Given this, the objective of this study was to investigate the contribution of the NRF2-ARE pathway in the redox adaptation of patients with AF under different conditions of pain crises in the last year before the start of the research, with patients without pain crises (SC, n=14), low frequency (BFC, n=7; 1 to 2 crises), and high frequency (AFC, n=4; more than six crises). Hematological analyses were performed, as well as an evaluation of the relative expression (qPCR) of the NFE2L2, SOD1, CAT, GPX1, TXNRD1, and GSR genes and the enzymatic activities of Cat, Gpx, Gr, GST, and G6PDH by spectrophotometry. The data were submitted to normality tests, univariate analyses (ANOVA or Kruskal-Wallis), correlations (Pearson or Spearman), and multivariate analysis (PLS-DA). Hematological characterization did not reveal statistically significant differences between the groups, although the AFC group showed a pattern of reduced hemoglobin and hematocrit. PLS-DA analysis demonstrated considerable overlap of hematological variables, gene expression, and enzyme activity between the groups evaluated. Among the genes studied, only SOD1 showed lower expression in the groups with higher seizure frequency (p