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Buelna-Chontal M.,National Institute Of Cardiology I Ch | Guevara-Chavez J.-G.,National Institute Of Cardiology I Ch | Silva-Palacios A.,National Institute Of Cardiology I Ch | Medina-Campos O.-N.,National Autonomous University of Mexico | And 2 more authors.
Free Radical Biology and Medicine | Year: 2014

Postconditioning (PostC) activates endogenous protective mechanisms that contend against reperfusion injury. Nevertheless, although PostC efficiency in both experimental studies and clinical trials has been demonstrated, a complete picture of the interacting mechanisms, particularly the relationship between kinase signaling and redox maintenance, is still lacking. To unravel such association, in this work we focus on the participation of protein kinase C (PKC) and the transcription factor nuclear factor E2-related factor 2 (Nrf2) in the cardioprotective response elicited by PostC. PostC was performed in an in vivo rat model by applying three repetitive cycles of ischemia and reperfusion (10 s each), followed by evaluation of heart function and infarct size measurements. PKC activation and Nrf2 phosphorylation were evaluated after 10 min of reperfusion, whereas Nrf2 activity and the content and activities of Nrf2-regulated antioxidant proteins were evaluated after 60 min of reperfusion in PostC hearts. Maintenance of heart function and diminution in infarct size concurred with PKC activation and Nrf2 phosphorylation. PKC inhibition diminished Nrf2 phosphorylation and transcriptional activity in association with diminished levels and activities of Nrf2-regulated antioxidant proteins. In conclusion, this study proposes that the novel pathway PKC/Nrf2 participates in the long-term protective mechanisms induced by PostC application by maintaining the antioxidant defense system. © 2014 Elsevier Inc.

Tapia E.,National Institute Of Cardiology I Ch | Tapia E.,National Institute Of Cardiology I Ch | Sanchez-Lozada L.G.,National Institute Of Cardiology I Ch | Sanchez-Lozada L.G.,National Institute Of Cardiology I Ch | And 18 more authors.
Free Radical Research | Year: 2014

The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl β-D-glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production. © 2014 Informa UK, Ltd.

Hernandez-Resendiz S.,National Institute Of Cardiology I Ch | Correa F.,National Institute Of Cardiology I Ch | Garcia-Nino W.R.,National Institute Of Cardiology I Ch | Garcia-Nino W.R.,National Autonomous University of Mexico | And 8 more authors.
Cardiovascular Drugs and Therapy | Year: 2015

Purpose: The pathogenic mechanisms leading to cardiovascular disorders in patients with chronic kidney disease have not been clearly established, although increased oxidative stress has been pointed out as a potential cause. Therefore, as cardiovascular events are still the first cause of death in patients with chronic kidney disease and traditional drugs or therapies rarely have effects on cardiac complications, we sought to determine the effect of curcumin in treating cardiac dysfunction in rats with established chronic renal disease. Methods and Results: Treatment consisted in daily administration of curcumin (120 mg/kg/day) dissolved in 0.05 % carboxymethylcellulose via oral gavages during 30 days, beginning from day 30 after 5/6 nephrectomy (5/6Nx). Cardiac function, markers of oxidative stress, activation of PI3K/Akt/GSK3β and MEK1/2-ERK1/2 pathway, metalloproteinase-II (MMP-2) content, overall gelatinolytic activity, ROS production and mitochondrial integrity were evaluated after 1-month treatment. Curcumin restored systolic blood pressure, diminished interventricular and rear wall thickening, decreased left ventricle dimension at end-systole (LVSd) and restored ejection fraction in nephrectomized rats. Also, it diminished metalloproteinase-II levels and overall gelatinase activity, decreased oxidative stress and inhibited the mitochondrial permeability transition pore opening. Conclusion: Our findings suggest that curcumin might have therapeutic potential in treatment of heart disease in patients with established CKD by attenuating oxidative stress-related events as cardiac remodeling, mitochondrial dysfunction and cell death. © 2015, Springer Science+Business Media New York.

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