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.
Abe
Masahiro
M
Department of Clinical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. abe19791016@yahoo.co.jp <abe19791016@yahoo.co.jp>
Takiguchi
Yoshiharu
Y
Ichimaru
Satoshi
S
Kaji
Shinichiro
S
Tsuchiya
Koichiro
K
Wada
Koichiro
K
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