title: Curcumin prevents cisplatin-induced decrease in the tight and adherens junctions: relation to oxidative stress.
abstract: Curcumin is a polyphenol and cisplatin is an antineoplastic agent that induces nephrotoxicity associated with oxidative stress, apoptosis, fibrosis and decrease in renal tight junction (TJ) proteins. The potential effect of curcumin against alterations in TJ structure and function has not been evaluated in cisplatin-induced nephrotoxicity. The present study explored whether curcumin is able to prevent the cisplatin-induced fibrosis and decreased expression of the TJ and adherens junction (AJ) proteins occludin, claudin-2 and E-cadherin in cisplatin-induced nephrotoxicity. Curcumin (200 mg kg(-1)) was administered in three doses, and rats were sacrificed 72 h after cisplatin administration. Curcumin was able to scavenge, in a concentration-dependent way, superoxide anion, hydroxyl radical, peroxyl radical, singlet oxygen, peroxynitrite anion, hypochlorous acid and hydrogen peroxide. Cisplatin-induced renal damage was associated with alterations in plasma creatinine, expression of neutrophil gelatinase-associated lipocalin and of kidney injury molecule-1, histological damage, increase in apoptosis, fibrosis (evaluated by transforming growth factor β1, collagen I and IV and α-smooth muscle actin expressions), increase in oxidative/nitrosative stress (evaluated by Hsp70/72 expression, protein tyrosine nitration, superoxide anion production in isolated glomeruli and proximal tubules, and protein levels of NADPH oxidase subunits p47(phox) and gp91(phox), protein kinase C β2, and Nrf2) as well as by decreased expression of occludin, claudin-2, β-catenin and E-cadherin. Curcumin treatment prevented all the above-described alterations. The protective effect of curcumin against cisplatin-induced fibrosis and decreased proteins of the TJ and AJ was associated with the prevention of glomerular and proximal tubular superoxide anion production induced by NADPH oxidase activity.
authors.affiliation: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), 04510 University City, D.F., Mexico. pedraza@unam.mx.
authors.forename: Joyce
authors.initials: J
authors.lastname: Trujillo
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City, 07360, Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Molina-Jijón
authors.affiliation: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), 04510 University City, D.F., Mexico. pedraza@unam.mx.
authors.forename: Omar Noel
authors.initials: ON
authors.lastname: Medina-Campos
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City, 07360, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rodríguez-Muñoz
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City, 07360, Mexico.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Reyes
authors.affiliation: School of Medicine, Panamericana University, Mexico City, 03920, Mexico.
authors.forename: María L
authors.initials: ML
authors.lastname: Loredo
authors.affiliation: Department of Pharmacology, Faculty of Medicine, National Autonomous University of Mexico (UNAM), University City, 04510, Mexico.
authors.forename: Diana
authors.initials: D
authors.lastname: Barrera-Oviedo
authors.affiliation: Animal Care Unit, Faculty of Medicine, National Autonomous University of Mexico (UNAM), University City, 04510, Mexico.
authors.forename: Enrique
authors.initials: E
authors.lastname: Pinzón
authors.affiliation: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), 04510 University City, D.F., Mexico. pedraza@unam.mx.
authors.forename: Daniela Saraí
authors.initials: DS
authors.lastname: Rodríguez-Rangel
authors.affiliation: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), 04510 University City, D.F., Mexico. pedraza@unam.mx.
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverri
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D015415:Biomarkers; D002945:Cisplatin / Q000633:toxicity*; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D005355:Fibrosis / Q000188:drug therapy; D016166:Free Radical Scavengers; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D019255:NADPH Oxidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D064546:Protein Kinase C beta / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides; D019108:Tight Junctions / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016166:Free Radical Scavengers; D021122:Protein Subunits; D017382:Reactive Oxygen Species; D013481:Superoxides; D019255:NADPH Oxidases; D064546:Protein Kinase C beta; D003474:Curcumin; D002945:Cisplatin