Indoxyl sulfate and p-cresyl sulfate in chronic kidney disease. Could these toxins modulate the antioxidant Nrf2-Keap1 pathway?
Protein-bound uremic toxins (i.e., indoxyl sulfate or p-cresyl sulfate), produced by intestinal bacteria, are accumulated in the plasma of chronic kidney disease (CKD) patients. These toxins interact negatively with biological functions, having potent oxidative stress-inducing effects and a pathological effect on cardiovascular disease. Recent research in CKD has shown that oxidative stress and inflammation can be compounded by impaired activation of the nuclear factor (erythroid-2-related factor)-2 (Nrf2)-Kelch-like ECH associating protein-1 (Keap1) pathway, a major cellular defense mechanism. However, to date, many questions arise regarding the role of this system in CKD. For example, protein-bound uremic toxins promote oxidative stress in CKD patients, but their putative effect on the Nrf2-Keap1 system has yet to be examined in these patients. This review will focus on the putative relationship among protein-bound uremic toxins, oxidative stress, and a possible decreased expression of Nrf2 in CKD.
Cardiovascular Sciences Graduate Program, Federal University Fluminense, Niterói-Rio de Janeiro, Brazil. Electronic address: milbarcza@gmail.com.
Milena Barcza
MB
Stockler-Pinto
Department of Nephrology, Centre Hopitalier Lyon Sud, INSERM 1060, CENS, Université de Lyon, France.
Denis
D
Fouque
Université de Lyon, INSA de Lyon, CarMeN, INSERM U1060, Villeurbanne, France.
Christophe O
CO
Soulage
Université de Lyon, INSA de Lyon, CarMeN, INSERM U1060, Villeurbanne, France.
Marine
M
Croze
Cardiovascular Sciences Graduate Program, Federal University Fluminense, Niterói-Rio de Janeiro, Brazil.
Denise
D
Mafra
D000975:Antioxidants / Q000378:metabolism*; D003408:Cresols / Q000097:blood*; D005786:Gene Expression Regulation; D006801:Humans; D007200:Indican / Q000097:blood*; D007249:Inflammation / Q000097:blood; D007422:Intestines / Q000382:microbiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072019:Kelch-Like ECH-Associated Protein 1; D064307:Microbiota / Q000502:physiology; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D015398:Signal Transduction; D013463:Sulfuric Acid Esters / Q000097:blood*
D000975:Antioxidants; D003408:Cresols; 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; D017382:Reactive Oxygen Species; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate; D007200:Indican