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Curcumin prevents mitochondrial dynamics disturbances in early 5/6 nephrectomy: Relation to oxidative stress and mitochondrial bioenergetics.

Authors: Aparicio-Trejo, Omar Emiliano  Tapia, Edilia  Molina-Jijón, Eduardo  Medina-Campos, Omar Noel  Macías-Ruvalcaba, Norma Angélica  León-Contreras, Juan Carlos  Hernández-Pando, Rogelio  García-Arroyo, Fernando E  Cristóbal, Magdalena  Sánchez-Lozada, Laura Gabriela  Pedraza-Chaverri, José 
Citation: Aparicio-Trejo OE, etal., Biofactors. 2016 Nov 1. doi: 10.1002/biof.1338.
Pubmed: (View Article at PubMed) PMID:27801955
DOI: Full-text: DOI:10.1002/biof.1338

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, 00(00):000000, 2016.


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CRRD Object Information
CRRD ID: 12738369
Created: 2017-02-01
Species: All species
Last Modified: 2017-02-01
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.