title: Epicatechin regulation of mitochondrial structure and function is opioid receptor dependent.
abstract: METHODS
  The flavanol (-)-epicatechin (Epi), a component of cacao, has cardiac protective benefits in humans. Our previous study demonstrated Epi has δ-opioid receptor (DOR) binding activity and promotes cardiac protection. Here we examined the effects of 10 days of Epi treatment on: cardiac mitochondrial respiration, reactive oxygen species production, calcium swelling, and mitochondrial membrane fluidity.
  
  
  RESULTS
  Mice were randomized into four groups: (i) control (saline), (ii) naltrindole (Nalt; DOR antagonist), (iii) Epi, and (iv) Epi + Nalt and received 1 mg/kg Epi or water via oral gavage. Nalt groups received 5 mg/kg ip per day for 10 days. Significant increases in mitochondrial respiration and enhanced free radical production during state 3 respiration were observed with Epi. Additionally, we observed significant increases in rigidity of mitochondrial membranes and resistance to calcium-induced mitochondrial swelling with Epi treatment. Blocking the DOR with Nalt resulted in decreases in all of the observed parameters by Epi treatment.
  
  
  CONCLUSIONS
  These findings indicate that Epi induces an integrated response that includes metabolic and structural changes in cardiac mitochondria resulting in greater functional capacity via DOR. Mitochondrial targeted effects of epicatechin may explain the physiologic benefit observed on cardiac protection and support epicatechin's potential clinical application as a cardiac protective mimetic.
authors.affiliation: Department of Anesthesiology, University of California, San Diego, CA 92161, USA.
authors.forename: Mathivadhani
authors.initials: M
authors.lastname: Panneerselvam
authors.forename: Sameh S
authors.initials: SS
authors.lastname: Ali
authors.forename: J Cameron
authors.initials: JC
authors.lastname: Finley
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Kellerhals
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Migita
authors.forename: Brian P
authors.initials: BP
authors.lastname: Head
authors.forename: Piyush M
authors.initials: PM
authors.lastname: Patel
authors.forename: David M
authors.initials: DM
authors.lastname: Roth
authors.forename: Hemal H
authors.initials: HH
authors.lastname: Patel
mesh_terms: D000818:Animals; D002099:Cacao / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D002392:Catechin / Q000008:administration & dosage / Q000494:pharmacology*; D019069:Cell Respiration / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D017465:Receptors, Opioid, delta; D002392:Catechin; D002118:Calcium