PMID- 26997724
OWN - NLM
STAT- MEDLINE
DCOM- 20170109
LR  - 20181202
IS  - 1998-3751 (Electronic)
IS  - 0253-7613 (Print)
IS  - 0253-7613 (Linking)
VI  - 48
IP  - 1
DP  - 2016 Jan-Feb
TI  - Effect of pioglitazone on the abrogated cardioprotective effect of ischemic 
      preconditioning in hyperlipidemic rat heart.
PG  - 59-63
LID - 10.4103/0253-7613.174545 [doi]
AB  - OBJECTIVES: The signaling pathways upstream of glycogen synthase kinase-3beta 
      (GSK-3beta) get reduced during ischemic preconditioning (IPC) in hyperlipidemic rat 
      heart. Pioglitazone, an insulin sensitizer, exerts cardioprotection through 
      GSK-3beta. The objective of the study is to investigate the role of pioglitazone on 
      the attenuated cardioprotective effect of IPC in hyperlipidemic rat heart. 
      MATERIALS AND METHODS: The rats were administered high-fat diet for 8 weeks to 
      induce experimental hyperlipidemia (HL). After mounting on a Langendorff 
      apparatus, isolated perfused hearts were given four cycles of IPC; each consists 
      of 5 min of both ischemia and reperfusion followed by 30 min of ischemia and 120 
      min of reperfusion. Insulin (50 mU/ml) was perfused alone and in combination with 
      pioglitazone (2 muM), while in other groups, this combination was repeated with 
      wortmannin (100 nM), a selective PI3K inhibitor and rapamycin (1 nM), a selective 
      mammalian target of rapamycin (mTOR) inhibitor, separately, and in combination. 
      Myocardial injury was assessed by measuring infarct size and the levels of 
      creatinine kinase-myocardial band (CK-MB) and lactate dehydrogenase (LDH) in the 
      coronary effluent. RESULTS: IPC significantly decreased the infarct size and 
      levels of LDH and CK-MB in normal but not in HL rat heart. Perfusion of insulin 
      along with pioglitazone significantly reduced the infarct size and release of 
      CK-MB and LDH in IPC-treated HL rat hearts. Perfusion of wortmannin or rapamycin 
      alone significantly and in combination almost completely abolished the 
      pioglitazone-induced restored cardioprotection (P < 0.05). CONCLUSION: 
      Cardioprotective effect of IPC gets lost in hyperlipidemic rat heart. The results 
      suggest that perfusion of pioglitazone restored the cardioprotective effect of 
      IPC in hyperlipidemic rat heart, an effect that may be via PI3K and mTOR.
FAU - Mittal, Dhiraj
AU  - Mittal D
AD  - Department of Pharmacology, I.S.F. College of Pharmacy, Moga, Punjab, India.
FAU - Taliyan, Rajeev
AU  - Taliyan R
AD  - Department of Pharmacy, BITS, Pilani, Rajasthan, India.
FAU - Sharma, P L
AU  - Sharma PL
AD  - Department of Pharmacology, I.S.F. College of Pharmacy, Moga, Punjab, India.
FAU - Yadav, Harlokesh Narayan
AU  - Yadav HN
AD  - Department of Pharmacology AIIMS, New Delhi, India.
LA  - eng
PT  - Journal Article
PL  - India
TA  - Indian J Pharmacol
JT  - Indian journal of pharmacology
JID - 7902477
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Triglycerides)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - X4OV71U42S (Pioglitazone)
SB  - IM
MH  - Animals
MH  - Cardiotonic Agents/*pharmacology
MH  - Cholesterol/blood
MH  - Diet, High-Fat
MH  - Female
MH  - Heart/*drug effects
MH  - Hyperlipidemias/*blood
MH  - Hypoglycemic Agents/*pharmacology
MH  - *Ischemic Preconditioning
MH  - Male
MH  - Pioglitazone
MH  - Rats
MH  - Rats, Wistar
MH  - Thiazolidinediones/*pharmacology
MH  - Triglycerides/blood
PMC - PMC4778209
OTO - NOTNLM
OT  - Creatinine kinase
OT  - glycogen synthase kinase-3beta
OT  - ischemia-reperfusion
OT  - lactate dehydrogenase
OT  - myocardial injury
OT  - pioglitazone
OT  - rapamycin
OT  - wortmannin
EDAT- 2016/03/22 06:00
MHDA- 2017/01/10 06:00
PMCR- 2016/01/01
CRDT- 2016/03/22 06:00
PHST- 2016/03/22 06:00 [entrez]
PHST- 2016/03/22 06:00 [pubmed]
PHST- 2017/01/10 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - IJPharm-48-59 [pii]
AID - 10.4103/0253-7613.174545 [doi]
PST - ppublish
SO  - Indian J Pharmacol. 2016 Jan-Feb;48(1):59-63. doi: 10.4103/0253-7613.174545.