title: The uremic toxin indoxyl sulfate exacerbates reactive oxygen species production and inflammation in 3T3-L1 adipose cells.
abstract: Inflammation and oxidative stress are common features of patients with chronic kidney disease (CKD) and many uremic solutes retained in these patients could be involved in these processes, among which protein-bound solutes such as indoxyl sulfate (IS). White adipose tissue recently gained attention as an important source of inflammation and oxidative stress. To examine the effect of IS on adipocytes, 3T3-L1 adipose cells were incubated with IS to mimic the conditions encountered in uremic patients. Incubation of adipose cells with IS increased reactive oxygen species production generated mainly through activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase since it was prevented by the NADPH oxidase inhibitor apocynin. Exposure to IS furthermore exacerbated the secretion of tumor necrosis factor-α and interleukin-6 by adipose cells. This inflammatory response was prevented by NADPH oxidase inhibition pinpointing the pivotal role of intracellular oxidative stress. IS induces adipocyte perturbation and promotes inflammatory state mainly through induction of oxidative stress. IS, a uremic toxin, accumulates in CKD patients could, therefore, be an important mediator of adipocyte dysfunction in these patients.
authors.affiliation: a Cardiovascular Sciences Graduate Program, Federal Fluminense University , Niterói , Brazil ;
authors.forename: Milena B
authors.initials: MB
authors.lastname: Stockler-Pinto
authors.affiliation: b Medical Sciences Graduate Program, Federal Fluminense University , Niterói , Brazil ;
authors.forename: Juliana F
authors.initials: JF
authors.lastname: Saldanha
authors.affiliation: c Université De Lyon, INSA De Lyon, CarMeN, INSERM U1060 , Villeurbanne , France ;
authors.forename: Dan
authors.initials: D
authors.lastname: Yi
authors.affiliation: a Cardiovascular Sciences Graduate Program, Federal Fluminense University , Niterói , Brazil ;|b Medical Sciences Graduate Program, Federal Fluminense University , Niterói , Brazil ;
authors.forename: Denise
authors.initials: D
authors.lastname: Mafra
authors.affiliation: c Université De Lyon, INSA De Lyon, CarMeN, INSERM U1060 , Villeurbanne , France ;|d Department of Nephrology , Centre Hopitalier Lyon Sud , Pierre-Bénite , France.
authors.forename: Denis
authors.initials: D
authors.lastname: Fouque
authors.affiliation: c Université De Lyon, INSA De Lyon, CarMeN, INSERM U1060 , Villeurbanne , France ;
authors.forename: Christophe O
authors.initials: CO
authors.lastname: Soulage
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D007200:Indican / Q000494:pharmacology*; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D019255:NADPH Oxidases / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000494:pharmacology; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D014118:Toxins, Biological / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014511:Uremia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
chemical_list: D015850:Interleukin-6; D017382:Reactive Oxygen Species; D014118:Toxins, Biological; D014409:Tumor Necrosis Factor-alpha; D019255:NADPH Oxidases; D007200:Indican
keywords: Antioxidant; cardiovascular; cytokines