Abstract:
:The present study was designed to investigate the modulatory effects of rottlerin on ischemia reperfusion induced myocardial injury. Isolated rat hearts were exposed to 30 min of global ischemia followed by 120 min of reperfusion using Langendorff apparatus. Myocardial injury was assessed in the terms of infarct size, release of lactate dehydrogenase (LDH), creatine kinase (CK) enzymes. Rottlerin, a selective PKCdelta inhibitor, did not modulate ischemia-reperfusion (I/R) induced myocardial injury at low dose (3 microM). However, at moderate dose (6 microM) it significantly produced cardioprotective effects. On the contrary, rottlerin at high dose (12 microM) significantly enhanced I/R induced myocardial injury. However, administration of FR-167653 (1.1 microM, 2.2 microM), a selective p-38 mitogen activated protein kinase (p-38 MAPK) inhibitor, attenuated rottlerin (12 microM) mediated enhancement in I/R induced myocardial injury in a dose dependent manner. Per se administration of FR-167653 (1.1 microM, 2.2 microM) also attenuated I/R induced myocardial injury in a dose dependent manner. Pretreatment with rottlerin (6 microM) did not enhance the cardioprotective effects of FR-167653 (2.2 microM). It may be concluded that rottlerin mediated cardioprotective effects at moderate dose, possible due to inhibition of PKCdelta; while at high dose it enhanced I/R induced myocardial injury which may be attributed to activation of p-38 MAPK.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Kaur K,Singh M,Singh N,Jaggi ASdoi
10.1248/bpb.31.1745subject
Has Abstractpub_date
2008-09-01 00:00:00pages
1745-8issue
9eissn
0918-6158issn
1347-5215pii
JST.JSTAGE/bpb/31.1745journal_volume
31pub_type
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
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