Portal de Periódicos da CAPES

Oxidative stress and inflammatory response evoked by transient cerebral ischemia/reperfusion: Effects of the PPAR-α agonist WY14643

2006; Elsevier BV; Volume: 41; Issue: 4 Linguagem: Inglês

10.1016/j.freeradbiomed.2006.04.030

1873-4596

Massimo Collino, Manuela Aragno, Raffaella Mastrocola, Elisa Benetti, Margherita Gallicchio, Chiara Dianzani, Oliviero Danni, Christoph Thiemermann, Roberto Fantozzi,

Eicosanoids and Hypertension Pharmacology

This study investigated the effects of the selective peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist WY14643 on ischemia/reperfusion (I/R) injury in the rat hippocampus. Transient cerebral ischemia (30 min), followed by 1-24 h reperfusion, significantly increased the generation of reactive oxygen species, nitric oxide (NO), and lipid peroxidation end-products, as well as markedly reducing levels of the endogenous antioxidant glutathione. Reperfusion for 3-6 h led to increased expression of the proteins heme oxygenase-1 (HO-1), cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1). Pretreatment with WY14643 suppressed oxidative stress and expression of HO-1, iNOS, and ICAM-1, but had no effect on COX-2. These effects are due to suppression of the activation of p38 mitogen-activated protein kinase and nuclear factor-kappaB. The PPAR-alpha antagonist MK886 abolished the beneficial effects of WY14643. The levels of S100B protein, a marker of cerebral injury used in stroke trials to monitor injury, were high in the hippocampus of rats exposed to I/R, but markedly reduced by WY14643. We propose that WY14643 protects the brain against excessive oxidative stress and inflammation and may thus be useful in treating stroke.