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Fenofibrate attenuates impaired ischemic preconditioning-mediated cardioprotection in the fructose-fed hypertriglyceridemic rat heart.
MedLine Citation:
PMID:  23325365     Owner:  NLM     Status:  Publisher    
We investigated in this study whether or not the ischemic preconditioning (IPC)-mediated cardioprotective effect against ischemia-reperfusion (I/R) injury exists in the fructose-fed hypertriglyceridemic (HTG) rat heart. Langendorff-perfused normal and fructose-fed (10 % w/v in drinking water, 8 weeks) HTG rat hearts were subjected to 30-min global ischemia and 120-min reperfusion. IPC protocol included four brief episodes (5 min each) of ischemia and reperfusion. Myocardial infarct size using triphenyltetrazolium chloride staining, markers of cardiac injury such as lactate dehydrogenase (LDH) and creatine kinase (CK-MB) release, coronary flow rate (CFR), and myocardial oxidative stress were assessed. High degree of myocardial I/R injury, by means of significant myocardial infarct size, elevated coronary LDH and CK-MB release, reduced CFR, and high oxidative stress, was noted in the HTG rat heart as compared to the normal rat heart. The IPC-mediated cardioprotection against I/R injury was markedly impaired in the HTG rat heart as compared to the normal rat heart. Interestingly, pharmacological reduction of triglycerides using 8-week treatment protocol with fenofibrate (80 mg/kg/day, p.o.) restored the IPC effect in the HTG rat heart that was blunted by coinfusion, during the IPC reperfusion protocol, of a specific inhibitor of phosphoinositide-3-kinase (PI3-K), wortmannin (100 nM). The IPC failed to protect the HTG rat heart against I/R injury. Fenofibrate treatment reduced high triglycerides in the fructose-fed HTG rat and subsequently restored the cardioprotective effect of IPC.
Lalita Babbar; Nanjaian Mahadevan; Pitchai Balakumar
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-17
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  -     ISSN:  1432-1912     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Cardiovascular Pharmacology Division, Department of Pharmacology, Rajendra Institute of Technology and Sciences, Sirsa, 125 055, India.
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