title: (-)-Epicatechin rich cocoa mediated modulation of oxidative stress regulators in skeletal muscle of heart failure and type 2 diabetes patients.
abstract: BACKGROUND
  Type 2 diabetes (T2D) and heart failure (HF) are associated with high levels of skeletal muscle (SkM) oxidative stress (OS). Health benefits attributed to flavonoids have been ascribed to antioxidation. However, for flavonoids with similar antioxidant potential, end-biological effects vary widely suggesting other mechanistic venues for reducing OS. Decreases in OS may follow the modulation of key regulatory pathways including antioxidant levels (e.g. glutathione) and enzymes such as mitochondrial superoxide dismutase (SOD2) and catalase.
  
  
  METHODS
  We examined OS-related alterations in SkM in T2D/HF patients (as compared vs. healthy controls) and evaluated the effects of three-month treatment with (-)-epicatechin (Epi) rich cocoa (ERC). To evidence Epi as the mediator of the improved OS profile we examined the effects of pure Epi (vs. water) on SkM OS regulatory systems in a mouse model of insulin resistance and contrasted results vs. normal mice.
  
  
  RESULTS
  There were severe alterations in OS regulatory systems in T2D/HF SkM as compared with healthy controls. Treatment with ERC induced recovery in glutathione levels and decreases in the nitrotyrosilation and carbonylation of proteins. With treatment, key transcriptional factors translocate into the nucleus leading to increases in SOD2 and catalase protein expression and activity levels. In insulin resistant mice, there were alterations in muscle OS and pure Epi replicated the beneficial effects of ERC found in humans.
  
  
  CONCLUSIONS
  Major perturbations in SkM OS can be reversed with ERC in T2D/HF patients. Epi likely mediates such effects and may provide an effective means to treat conditions associated with tissue OS.
authors.affiliation: Escuela Superior de Medicina del Instituto Politécnico Nacional, Seccion de Posgrado, Mexico City, Mexico.
authors.forename: Israel
authors.initials: I
authors.lastname: Ramirez-Sanchez
authors.affiliation: University of California, San Diego, School of Medicine, Seccion de Posgrado, Mexico City,Mexico.
authors.forename: Pam R
authors.initials: PR
authors.lastname: Taub
authors.affiliation: University of California, San Diego, School of Medicine, Seccion de Posgrado, Mexico City,Mexico.|VA San Diego Healthcare System, Seccion de Posgrado, Mexico City, Mexico.
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Ciaraldi
authors.affiliation: University of California, San Diego, School of Medicine, Seccion de Posgrado, Mexico City,Mexico.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Nogueira
authors.affiliation: University of California, San Diego, School of Medicine, Seccion de Posgrado, Mexico City,Mexico.
authors.forename: Taylor
authors.initials: T
authors.lastname: Coe
authors.affiliation: University of California, San Diego, School of Medicine, Seccion de Posgrado, Mexico City,Mexico.
authors.forename: Guy
authors.initials: G
authors.lastname: Perkins
authors.affiliation: University of California, San Diego, School of Medicine, Seccion de Posgrado, Mexico City,Mexico.
authors.forename: Michael
authors.initials: M
authors.lastname: Hogan
authors.affiliation: University of California, San Diego, School of Medicine, Seccion de Posgrado, Mexico City,Mexico.|VA San Diego Healthcare System, Seccion de Posgrado, Mexico City, Mexico.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Maisel
authors.affiliation: University of California, San Diego, School of Medicine, Seccion de Posgrado, Mexico City,Mexico.|VA San Diego Healthcare System, Seccion de Posgrado, Mexico City, Mexico.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
authors.affiliation: Escuela Superior de Medicina del Instituto Politécnico Nacional, Seccion de Posgrado, Mexico City, Mexico.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ceballos
authors.affiliation: University of California, San Diego, School of Medicine, Seccion de Posgrado, Mexico City,Mexico.
authors.forename: Francisco
authors.initials: F
authors.lastname: Villarreal
mesh_terms: D000368:Aged; D000818:Animals; D001628:Beverages; D002099:Cacao; D002392:Catechin / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010865:Pilot Projects
chemical_list: D002392:Catechin
keywords: (−)-epicatechin; (−)-epicatechin rich cocoa; 2,4-dinitrophenyldrazone; Cocoa; DNP; ERC; Epi; Epicatechin; FOXO1; Flavanols; GAPDH; HF; HFD; IP; OS; PGC1α; ROS; S6 ribosomal protein; S6RP; SIRT; SOD2; SkM; T2D; WB; forkhead box protein O1; glyceraldehyde 3-phosphate dehydrogenase; heart failure; high fat diet; immunoprecipitation; oxidative stress; peroxisome proliferator-activated receptor gamma coactivator 1-α; reactive oxygen species; sirtuin; skeletal muscle; superoxide dismutase-2; type 2 diabetes; western blotting