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Co-administration of the flavanol (-)-epicatechin with doxycycline synergistically reduces infarct size in a model of ischemia reperfusion injury by inhibition of mitochondrial swelling.
MedLine Citation:
PMID:  25281837     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
(-)-Epicatechin (EPI) is cardioprotective in the setting of ischemia/reperfusion (IR) injury and doxycycline (DOX) is known to preserve cardiac structure/function after myocardial infarction (MI). The main objective of this study was to examine the effects of EPI and DOX co-administration on MI size after IR injury and to determine if cardioprotection may involve the mitigation of mitochondrial swelling. For this purpose, a rat model of IR was used. Animals were subjected to a temporary 45min occlusion of the left anterior descending coronary artery. Treatment consisted of a single or double dose of EPI (10mg/kg) combined with DOX (5mg/kg). The first dose was given 15min prior to reperfusion and the second 12h post-MI. The effects of EPI +/- DOX on mitochondrial swelling (i.e. mPTP opening) were determined using isolated mitochondria exposed to calcium overload and data examined using isobolographic analysis. To ascertain for the specificity of EPI effects on mitochondrial swelling other flavonoids were also evaluated. Single dose treatment reduced MI size by ∼46% at 48h and 44% at three weeks. Double dosing evidenced a synergistic, 82% reduction at 3 weeks. EPI plus DOX also inhibited mitochondrial swelling in a synergic manner thus, possibly accounting for the cardioprotective effects whereas limited efficacy was observed with the other flavonoids. Given the apparent lack of toxicity in humans, the combination of EPI and DOX may have clinical potential for the treatment of myocardial IR injury.
Authors:
Pilar Ortiz-Vilchis; Katrina Go Yamazaki; Ivan Rubio-Gayosso; Israel Ramirez-Sanchez; Claudia Calzada; Diego Romero-Perez; Alicia Ortiz; Eduardo Meaney; Pam Taub; Francisco Villarreal; Guillermo Ceballos
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-1
Journal Detail:
Title:  European journal of pharmacology     Volume:  -     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-4     Completed Date:  -     Revised Date:  2014-10-5    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier B.V.
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