Dietary and synthetic activators of the antistress gene response in treatment of renal disease.
Renal failure is associated with increased vascular inflammation, oxidative stress and dicarbonyl stress linked to development of cardiovascular disease, and other complications. The endogenous defense to inflammatory, oxidative, and dicarbonyl challenge to vascular function is coordinated by nuclear factor E2-related factor 2 (nrf2), kelch-related erythroid cell-derived protein with CNC homology (ECH) protein 1 (keap1), and antioxidant response element-linked gene expression in the antistress gene response. Intervention trials of the synthetic nrf2 activator, bardoloxone methyl, in patients with advanced diabetic nephropathy, showing improvement of renal function and decreased inflammation, suggest that nrf2 activators may have therapeutic benefit in chronic renal failure. Activators of nrf2 are of both synthetic and dietary origin. The aim of this review is to describe the "nrf2/keap1/antioxidant response element" transcriptional system and studies of this system in renal failure, and to assess the current status and future prospects that dietary nrf2 activators may be of benefit to patients with chronic renal failure.
Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, University Hospital, Coventry, United Kingdom. P.J.Thornalley@warwick.ac.uk
Paul J
PJ
Thornalley
Naila
N
Rabbani
D000818:Animals; D004032:Diet; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000502:physiology; D000072019:Kelch-Like ECH-Associated Protein 1; D007676:Kidney Failure, Chronic / Q000235:genetics*; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000502:physiology; D018384:Oxidative Stress / Q000235:genetics*
D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human