Modulation of the oxidative stress and inflammatory response by PPAR-γ agonists in the hippocampus of rats exposed to cerebral ischemia/reperfusion

• Published in: European journal of pharmacology 2006-01, Vol.530 (1), p.70-80
• Main Authors: Collino, Massimo, Aragno, Manuela, Mastrocola, Raffaella, Gallicchio, Margherita, Rosa, Arianna Carolina, Dianzani, Chiara, Danni, Oliviero, Thiemermann, Christopher, Fantozzi, Roberto
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain Ischemia - drug therapy; Brain Ischemia - physiopathology; Cyclooxygenase 2 - metabolism; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - physiopathology; Inflammation; Inflammation - drug therapy; Inflammation - physiopathology; Injections, Intravenous; Ischemia/reperfusion; Lipid Peroxidation - drug effects; Male; Medical sciences; Mitogen-Activated Protein Kinases - metabolism; Neurology; NF-kappa B - metabolism; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Pharmacology. Drug treatments; PPAR gamma - agonists; PPAR-γ (peroxisome proliferator-activated receptor-γ); PPAR-γ agonist; Rats; Rats, Wistar; Reperfusion Injury - drug therapy; Reperfusion Injury - physiopathology; Signal Transduction - drug effects; Thiazolidinediones - pharmacology; Thiazolidinediones - therapeutic use; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2005.11.049

Agonists of the peroxisome proliferator-activated receptor-γ (PPAR-γ) 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-γ 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-κB (NF-κB). Pre-treatment with either rosiglitazone or pioglitazone significantly reduced oxidative stress, COX-2 protein expression and activation of MAPKs and NF-κB. Taken together, the results provide convincing evidence that PPAR-γ agonists exert protective effects in a rat model of mild forebrain ischemia/reperfusion injury by inhibiting oxidative stress and excessive inflammatory response.