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Epicatechin regulation of mitochondrial structure and function is opioid receptor dependent
Author(s) -
Panneerselvam Mathivadhani,
Ali Sameh S.,
Finley J. Cameron,
Kellerhals Sarah E.,
Migita Michael Y.,
Head Brian P.,
Patel Piyush M.,
Roth David M.,
Patel Hemal H.
Publication year - 2013
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201300026
Subject(s) - mitochondrion , naltrindole , reactive oxygen species , respiration , inner mitochondrial membrane , chemistry , antagonist , pharmacology , receptor , medicine , opioid receptor , endocrinology , biology , biochemistry , anatomy
Scope 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. Methods and 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. Conclusion 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.