title: The nephroprotection exerted by curcumin in maleate-induced renal damage is associated with decreased mitochondrial fission and autophagy.
abstract: We have previously reported that the antioxidant curcumin exerts nephroprotection in maleate-induced renal damage, a model associated with oxidative stress. However, the mechanisms involved in curcumin protective effect were not explored, to assess this issue, curcumin was administered daily by gavage (150 mg/kg) five days before a single maleate (400 mg/kg)-injection. Curcumin prevented maleate-induced proteinuria, increased heat shock protein of 72 KDa (Hsp72) expression, and decreased plasma glutathione peroxidase activity. Maleate-induced oxidative stress by increasing the nicotinamide-adenine dinucleotide phosphate oxidase 4 (NOX4) and mitochondrial complex I-dependent superoxide anion (O2•-) production, formation of malondialdehyde (MDA)- and 3-nitrotyrosine (3-NT)-protein adducts and protein carbonylation and decreased GSH/GSSG ratio. Curcumin treatment ameliorated all the above-described changes. The maleate-induced epithelial damage, evaluated by claudin-2 and occludin expressions, was ameliorated by curcumin. It was found that maleate-induced oxidative stress promoted mitochondrial fission, evaluated by dynamin-related protein (Drp) 1 and fission (Fis) 1 expressions and by electron-microscopy, and autophagy, evaluated by phospho-threonine 389 from p70 ribosomal protein S6 kinase (p-Thr 389 p70S6K), beclin 1, microtubule-associated protein 1A/1B-light chain 3 phosphatidylethanolamine conjugate (LC3-II), autophagy-related gene 5 and 12 (Atg5-Atg12) complex, p62, and lysosomal-associated membrane protein (LAMP)-2 expressions in isolated proximal tubules and by electron-microscopy and LC-3 immunolabelling. Curcumin treatment ameliorated these changes. Moreover, curcumin alone induced autophagy in proximal tubules. These data suggest that the nephroprotective effect exerted by curcumin in maleate-induced renal damage is associated with decreased mitochondrial fission and autophagy. © 2016 BioFactors, 42(6):686-702, 2016.
authors.affiliation: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City, Mexico.|Department of Biociences and Engineering, CIIEMAD-IPN, Mexico City, 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), Mexico City, Mexico.
authors.forename: Omar Emiliano
authors.initials: OE
authors.lastname: Aparicio-Trejo
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rodríguez-Muñoz
authors.affiliation: Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán" (INCMNSZ), Tlalpan, Mexico City, Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: León-Contreras
authors.affiliation: Department of Physiology, Faculty of Medicine, National Autonomous University of Mexico (UNAM), Mexico City, Mexico.
authors.forename: María
authors.initials: M
authors.lastname: Del Carmen Cárdenas-Aguayo
authors.affiliation: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City, Mexico.
authors.forename: Omar Noel
authors.initials: ON
authors.lastname: Medina-Campos
authors.affiliation: Department of Nephrology and Laboratory of Renal Physiopathology, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico.
authors.forename: Edilia
authors.initials: E
authors.lastname: Tapia
authors.affiliation: Department of Nephrology and Laboratory of Renal Physiopathology, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico.
authors.forename: Laura Gabriela
authors.initials: LG
authors.lastname: Sánchez-Lozada
authors.affiliation: Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán" (INCMNSZ), Tlalpan, Mexico City, Mexico.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernández-Pando
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City, Mexico.
authors.forename: José L
authors.initials: JL
authors.lastname: Reyes
authors.affiliation: Department of Biociences and Engineering, CIIEMAD-IPN, Mexico City, Mexico.
authors.forename: Laura
authors.initials: L
authors.lastname: Arreola-Mendoza
authors.affiliation: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverri
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001343:Autophagy; D003474:Curcumin / Q000494:pharmacology*; D019610:Cytoprotection; D004353:Drug Evaluation, Preclinical; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008298:Maleates; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D063154:Mitochondrial Dynamics / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008298:Maleates; D017382:Reactive Oxygen Species; D003474:Curcumin
keywords: autophagy; curcumin; maleate; mitochondrial fission; oxidative stress; renal damage