title: Curcumin maintains cardiac and mitochondrial function in chronic kidney disease.
abstract: Curcumin, a natural pigment with antioxidant activity obtained from turmeric and largely used in traditional medicine, is currently being studied in the chemoprevention of several diseases for its pleiotropic effects and nontoxicity. In chronic renal failure, the pathogenic mechanisms leading to cardiovascular disorders have been associated with increased oxidative stress, a process inevitably linked with mitochondrial dysfunction. Thus, in this study we aimed at investigating if curcumin pretreatment exerts cardioprotective effects in a rat model of subtotal nephrectomy (5/6Nx) and its impact on mitochondrial homeostasis. Curcumin was orally administered (120mg/kg) to Wistar rats 7 days before nephrectomy and after surgery for 60 days (5/6Nx+curc). Renal dysfunction was detected a few days after nephrectomy, whereas changes in cardiac function were observed until the end of the protocol. Our results indicate that curcumin treatment protects against pathological remodeling, diminishes ischemic events, and preserves cardiac function in uremic rats. Cardioprotection was related to diminished reactive oxygen species production, decreased oxidative stress markers, increased antioxidant response, and diminution of active metalloproteinase-2. We also observed that curcumin's cardioprotective effects were related to maintaining mitochondrial function. Aconitase activity was significantly higher in the 5/6Nx + curc (408.5±68.7nmol/min/mg protein) than in the 5/6Nx group (104.4±52.3nmol/min/mg protein, P<0.05), and mitochondria from curcumin-treated rats showed enhanced oxidative phosphorylation capacities with both NADH-linked substrates and succinate plus rotenone (3.6±1 vs 1.1±0.9 and 3.1±0.7 vs 1.2±0.8, respectively, P<0.05). The mechanisms involved in cardioprotection included both direct antioxidant effects and indirect strategies that could be related to protein kinase C-activated downstream signaling.
authors.affiliation: Department of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Chavez, Mexico City, 14080 DF, Mexico; Department of Biochemistry, National Institute of Cardiology Ignacio Chavez, Mexico City, 14080 DF, Mexico.
authors.forename: Francisco
authors.initials: F
authors.lastname: Correa
authors.affiliation: Department of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Chavez, Mexico City, 14080 DF, Mexico; Department of Biochemistry, National Institute of Cardiology Ignacio Chavez, Mexico City, 14080 DF, Mexico.
authors.forename: Mabel
authors.initials: M
authors.lastname: Buelna-Chontal
authors.affiliation: Department of Biochemistry, National Institute of Cardiology Ignacio Chavez, Mexico City, 14080 DF, Mexico.
authors.forename: Sauri
authors.initials: S
authors.lastname: Hernández-Reséndiz
authors.affiliation: Renal Pathophysiology Laboratory, Department of Nephrology, National Institute of Cardiology Ignacio Chavez, Mexico City, 14080 DF, Mexico.
authors.forename: Wylly R
authors.initials: WR
authors.lastname: García-Niño
authors.affiliation: Department of Echocardiography, National Institute of Cardiology Ignacio Chavez, Mexico City, 14080 DF, Mexico.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Roldán
authors.affiliation: Department of Pathology, National Institute of Cardiology Ignacio Chavez, Mexico City, 14080, DF, Mexico.
authors.forename: Virgilia
authors.initials: V
authors.lastname: Soto
authors.affiliation: Department of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Chavez, Mexico City, 14080 DF, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Silva-Palacios
authors.affiliation: Department of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Chavez, Mexico City, 14080 DF, Mexico.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Amador
authors.affiliation: Department of Biology, Faculty of Chemistry, UNAM, Mexico City, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverrí
authors.affiliation: Renal Pathophysiology Laboratory, Department of Nephrology, National Institute of Cardiology Ignacio Chavez, Mexico City, 14080 DF, Mexico.
authors.forename: Edilia
authors.initials: E
authors.lastname: Tapia
authors.affiliation: Department of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Chavez, Mexico City, 14080 DF, Mexico; Department of Biochemistry, National Institute of Cardiology Ignacio Chavez, Mexico City, 14080 DF, Mexico. Electronic address: azazuetam@yahoo.com.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zazueta
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; D002374:Catalase; D003474:Curcumin
keywords: Cardiorenal dysfunction; Curcumin; Electrophile response element; Free radicals; Mitochondrial function; Oxidative stress