Expressão de Nrf2 e NFkB em pacientes renais crônicos em hemodiálise

Abstract

Oxidative stress and inflammation, important cardiovascular risk factors, are common features of patients with chronic kidney disease (CKD). Nuclear transcription factors are involved in these processes as NF&#61547;B which plays important role in the coordinate expression of inflammatory genes in these patients and the Keap1-Nrf2, which unlike NF&#61547;B operates in the genes promoter region coding for detoxifying enzymes stage II or antioxidant enzymes such as heme oxygenase 1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). The latter has emerged as important endogenous defense mechanism, incombat inflammation as well as oxidative stress, which may contribute to the improvement of cardiovascular complications of many diseases, including CKD. However, no study has evaluated to date this transcriptional factor in patients with CKD. The objective of this study was to evaluate the expression of Nfr2 and NF&#61547;B in patients on hemodialysis (HD). Twenty HD patients (55.0 ± 15.2 years, time of dialysis 76.5 ± 46.3 months, BMI 23.6 ± 3.0 kg/m2) were compared with 11 healthy subjects (50.9 ± 8.0 years, BMI 23.8 ± 1.9 kg/m2). Malondialdehyde (MDA) was measured by reaction with thiobarbituric acid. Peripheral blood mononuclear cells were isolated and analysis of real-time polymerase chain reaction was performed to evaluate mRNA levels of Nrf2, NF&#61547;B, NQO1 and HO-1. MDA levels were significantly higher in HD patients compared to the control group (13.2 ± 5.3 nmol/mL vs 5.1 ± 2.7 nmol/mL, p <0.01). The Nrf2 expression was lower in patients compared to healthy subjects (0.58 ± 0.35 vs 1.13 ± 0.64, p = 0.005). In contrast, the expression of NF&#61547;B was higher in this patients (2.18 ± 0.8 vs 1.04 ± 0.22, p = 0.0001). In addition, patients showed reduced expression of mRNA for NQO1 compared to healthy individuals. There was no difference in HO-1 expression. In patients, Nrf2 was negatively correlated with NF&#61547;B (r = -0.54, p = 0.014) and positive in healthy individuals (r = 0.77, p = 0.006). In conclusion, kidney patients on HD showed increased expression of NF&#61547;B and reduced expression of Nrf2 and NQO1, showing there is a possible imbalance in the transcriptional regulation of NF&#61547;B/Nrf2 in CKD patients on HD, which could increase the oxidative stress and inflammation in these patients