title: Curcumin prevents mitochondrial dynamics disturbances in early 5/6 nephrectomy: Relation to oxidative stress and mitochondrial bioenergetics.
abstract: Five-sixths nephrectomy (5/6NX) is a widely used model to study the mechanisms leading to renal damage in chronic kidney disease (CKD). However, early alterations on renal function, mitochondrial dynamics, and oxidative stress have not been explored yet. Curcumin is an antioxidant that has shown nephroprotection in 5/6NX-induced renal damage. The aim of this study was to explore the effect of curcumin on early mitochondrial alterations induced by 5/6NX in rats. In isolated mitochondria, 5/6NX-induced hydrogen peroxide production was associated with decreased activity of complexes I and V, decreased activity of antioxidant enzymes, alterations in oxygen consumption and increased MDA-protein adducts. In addition, it was found that 5/6NX shifted mitochondrial dynamics to fusion, which was evidenced by increased optic atrophy 1 and mitofusin 1 (Mfn1) and decreased fission 1 and dynamin-related protein 1 expressions. These data were confirmed by morphological analysis and immunoelectron microscopy of Mfn-1. All the above-described mechanisms were prevented by curcumin. Also, it was found that curcumin prevented renal dysfunction by improving renal blood flow and the total antioxidant capacity induced by 5/6NX. Moreover, in glomeruli and proximal tubules 5/6NX-induced superoxide anion production by uncoupled nitric oxide synthase (NOS) and nicotinamide adenine dinucleotide phosphate oxidase (NOX) dependent way, this latter was associated with increased phosphorylation of serine 304 of p47phox subunit of NOX. In conclusion, this study shows that curcumin pretreatment decreases early 5/6NX-induced altered mitochondrial dynamics, bioenergetics, and oxidative stress, which may be associated with the preservation of renal function. © 2016 BioFactors, 43(2):293-310, 2017.
authors: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City, 04510, Mexico.
authors: Omar Emiliano
authors: OE
authors: Aparicio-Trejo
authors: Department of Nephrology and Laboratory of Renal Pathophysiology, National Institute of Cardiology "Ignacio Chávez", Mexico City, 14080, Mexico.
authors: Edilia
authors: E
authors: Tapia
authors: Departamento de Biociencias e Ingeniería, Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y Desarrollo del Instituto Politécnico Nacional (CIIEMAD-IPN), Ciudad de México, 07340, México.
authors: Eduardo
authors: E
authors: Molina-Jijón
authors: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City, 04510, Mexico.
authors: Omar Noel
authors: ON
authors: Medina-Campos
authors: Department of Physical Chemistry, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City, 04510, Mexico.
authors: Norma Angélica
authors: NA
authors: Macías-Ruvalcaba
authors: Experimental Pathology Section, National Institute of Medical Sciences and Nutrition "Salvador Zubirán", Mexico City, 14000, Mexico.
authors: Juan Carlos
authors: JC
authors: León-Contreras
authors: Experimental Pathology Section, National Institute of Medical Sciences and Nutrition "Salvador Zubirán", Mexico City, 14000, Mexico.
authors: Rogelio
authors: R
authors: Hernández-Pando
authors: Department of Nephrology and Laboratory of Renal Pathophysiology, National Institute of Cardiology "Ignacio Chávez", Mexico City, 14080, Mexico.
authors: Fernando E
authors: FE
authors: García-Arroyo
authors: Department of Nephrology and Laboratory of Renal Pathophysiology, National Institute of Cardiology "Ignacio Chávez", Mexico City, 14080, Mexico.
authors: Magdalena
authors: M
authors: Cristóbal
authors: Department of Nephrology and Laboratory of Renal Pathophysiology, National Institute of Cardiology "Ignacio Chávez", Mexico City, 14080, Mexico.
authors: Laura Gabriela
authors: LG
authors: Sánchez-Lozada
authors: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City, 04510, Mexico.
authors: José
authors: J
authors: Pedraza-Chaverri
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D003474:Curcumin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D034281:Dynamins / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D063154:Mitochondrial Dynamics / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000096:biosynthesis; D009392:Nephrectomy / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008565:Membrane Proteins; C489709:Mfn1 protein, rat; D024101:Mitochondrial Proteins; C519851:Dnm1l protein, rat; D034281:Dynamins; D003474:Curcumin
keywords: 5/6 nephrectomy; curcumin; mitochondrial dynamics; mitochondrial dysfunction; mitochondrial fusion; oxidative stress