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Nuclear factor erythroid 2-related factor 2 (NRF2) is crucial in regulating cellular redox balance by increasing the expression of genes encoding antioxidant enzymes, such as heme oxygenase-1 (HO-1). However, patients with chronic kidney disease (CKD) have reduced NRF2 expression and overexpression of nuclear factor kappa B (NF-κB), a critical factor in pro-inflammatory responses. This imbalance contributes to CKD progression, cardiovascular outcomes, and high mortality rates. Sulforaphane (SFN), a bioactive compound found in cruciferous vegetables, is recognised as a natural NRF2 agonist and a potent anti-inflammatory agent. Therefore, the study aimed to evaluate the effects of SFN supplementation on the mRNA expression of NRF2 and NF-κB in non-dialysis CKD patients.
This was a longitudinal, double-blind, placebo-controlled study of 25 patients with CKD in stages 3-5. The patients were randomly allocated to the intervention group (2 capsules containing 200μg of SFN each per day) or the placebo group (2 capsules containing 200μg of cornstarch per day) for one month. Blood was collected in tubes containing EDTA as an anticoagulant. The expression of mRNA NRF2, NF-κB, and HO-1 in isolated peripheral blood mononuclear cells was assessed by real-time quantitative polymerase chain reaction.
All 25 patients completed the study: 10 in the intervention group (61.7 ± 10.0 years; BMI 27.5 ± 7.1 Kg/m2; 6 women; eGFR 44.3 ± 10.0 mL/min) and 15 in the placebo group (60.4 ± 11.9 years; BMI 30.0 ± 7.3 Kg/m2; 9 women; GFR 35.7 ± 12.0 mL/min). After supplementation, NRF2 mRNA expression increased significantly (p=0.02) (Table 1), and this difference was maintained when comparing the intervention and placebo groups after the intervention (change (∆) = 0.2, p=0.04). Furthermore, there was a statistical trend towards increased expression of HO-1 mRNA after SFN supplementation (p=0.07). No statistically significant difference was observed concerning the mRNA NF-κB expression (Table 1).
Table 1. mRNA expression of transcription factors and HO-1 before and after Sulforaphane intervention (Data expressed as mean (min-max).
One month of supplementation with 200 μg of SFN/day might improve the redox status of non-dialysis CKD patients by increasing the mRNA expression of NRF2 and the antioxidant enzyme HO-1.
Funding Sources: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ).