Modulation of the oxidative stress and inflammatory response by PPAR-gamma agonists in the hippocampus of rats exposed to cerebral ischemia/reperfusion.
Agonists of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) exert protective effects in several models of ischemia/reperfusion injury, but their role in stroke is less clear. The study investigates the effects of two PPAR-gamma agonists, rosiglitazone and pioglitazone, on oxidative stress and inflammatory response induced by ischemia/reperfusion in the rat hippocampus. Common carotid artery occlusion for 30 min followed by 1 h reperfusion resulted in a significant increase in the generation of reactive oxygen species, nitric oxide and the end products of lipid peroxidation as well as markedly reduced endogenous antioxidant glutathione levels and up-regulated superoxide dismutase activity. Western blot analysis showed that ischemia/reperfusion lead to an increase in cyclooxygenase-2 (COX-2) expression, as well activating p38 and p42/44 mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-kappaB). Pre-treatment with either rosiglitazone or pioglitazone significantly reduced oxidative stress, COX-2 protein expression and activation of MAPKs and NF-kappaB. Taken together, the results provide convincing evidence that PPAR-gamma agonists exert protective effects in a rat model of mild forebrain ischemia/reperfusion injury by inhibiting oxidative stress and excessive inflammatory response.
Collino
Massimo
M
Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Torino, Italy. massimo.collino@unito.it
Aragno
Manuela
M
Mastrocola
Raffaella
R
Gallicchio
Margherita
M
Rosa
Arianna Carolina
AC
Dianzani
Chiara
C
Danni
Oliviero
O
Thiemermann
Christopher
C
Fantozzi
Roberto
R
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D007275:Injections, Intravenous; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use
D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D000077205:Pioglitazone