Different effect of acute treatment with rosiglitazone on rat myocardial ischemia/reperfusion injury by administration method.
The present study was undertaken to examine the effect of rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, using different administration methods, on rat myocardial infarct size induced by 30 min of ischemia followed by 4 h of reperfusion. The infarct size was significantly reduced by the continuous infusion of rosiglitazone (0.5 mg/kg/h) from 30 min before occlusion for 2 h. On the other hand, limitation of the infarct size was shown by a bolus injection of 0.75 mg/kg at 5 min before reperfusion, but not by a bolus injection of 1 mg at 30 min before occlusion. The protective effect of rosiglitazone by the bolus injection before occlusion was obtained when an antioxidant, N-acetylcysteine, was concomitantly administered. The cardioprotection by rosiglitazone was associated with the inhibition of increased myeloperoxidase activity, tumor necrosis factor-alpha content and phosphorylation of inhibitor kappaB in the myocardium. The present study demonstrated that the protective effect of rosiglitazone on myocardial ischemia/reperfusion injury occurred most likely by inhibition of the nuclear factor-kappaB pathway through PPAR-gamma activation. However, acute treatment with rosiglitazone is harmful if its concentration is high during ischemia.
Department of Clinical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. abe19791016@yahoo.co.jp <abe19791016@yahoo.co.jp>
Masahiro
M
Abe
Yoshiharu
Y
Takiguchi
Satoshi
S
Ichimaru
Shinichiro
S
Kaji
Koichiro
K
Tsuchiya
Koichiro
K
Wada
D000111:Acetylcysteine / Q000008:administration & dosage; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D003198:Computer Simulation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D020672:I-kappa B Proteins / Q000378:metabolism; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation; D020011:Protective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D020672:I-kappa B Proteins; D016328:NF-kappa B; D047495:PPAR gamma; D020011:Protective Agents; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D009195:Peroxidase; D000111:Acetylcysteine