Edaravone Inhibits JNK-c-Jun Pathway and Restores Anti-oxidative Defense after Ischemia-Reperfusion Injury in Aged Rats(Pharmacology)

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概要

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• Edaravone, a potent antioxidant, is currently being used in the management of acute ischemic stroke in relatively high-aged populations. Mitogen activated protein kinase (MAPK) pathways have been shown to play important roles in neuronal cell death. We examined the role of MAPK pathways and the effect of treatment with edaravone in the brain after cerebral ischemia-reperfusion (I/R) injury in a bilateral carotid artery occlusion (BCAO) model with ischemia for 85 min followed by reperfusion for 45 min in aged rats. Western immunoblotting, immunostaining, enzyme-linked immunosorbent assay (ELISA), spectrophotometry, terminal deoxynucleotidyl transferase nick end labeling (TUNEL) and triphenyl tetrazolium chloride (TTC) staining were performed to evaluate various proteins in the homogenate, c-Jun NH_2-terminal kinase (JNK) in the tissue sections, protein carbonyl, glutathione peroxidase (GSHPx), apoptosis and infarct size, respectively. Our results showed that I/R injury resulted in a reduction of GSHPx, but protein carbonyl content and inducible nitric oxide synthase were increased. The activation of JNK and its downstream molecule c-Jun was significantly increased after injury, whereas the activities of p38 MAPK and extracellular-regulated kinase 1/2 were slightly but not significantly increased. Edaravone (3mg/kg, i.v.) treatment significantly reduced all of these changes. Our findings suggest that the JNK pathway differentially mediates neuronal injury in aged rats after BCAO, and edaravone treatment significantly reduces the neuronal damage after I/R injury by inhibiting oxidative stress and the JNK-c-Jun pathway with concomitant inhibition of overall MAPK activity in the brains of aged rats.

• 公益社団法人日本薬学会の論文
• 2006-04-01

著者

• Watanabe Kenichi

  Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences

• Watanabe Kenichi

  新潟大学 医歯学総合研究科循環器学

• Aizawa Yoshifusa

  First Department of Internal Medicine, Niigata University School of Medicine

• Kodama Makoto

  First Department of Internal Medicine, Division of Cardiology, Niigata University School of Medicine

• Kodama Makoto

  新潟大学 医歯学総合研究科循環器学

• MA Meilei

  Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharm

• Tachikawa Hitoshi

  Department of Cardiology, Niigata University School of Medicine

• Yamaguchi Kenichi

  Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical

• Ma Meilei

  Department Of Clinical Pharmacology Faculty Of Pharmaceutical Sciences Niigata University Of Pharmac

• Watanabe Kenichi

  Department Of Clinical Pharmacology Faculty Of Pharmaceutical Sciences Niigata University Of Pharmac

• Yamaguchi Kenichi

  Department Of Homeostatic Regulation And Development Niigata University Graduate School Of Medical A

• TACHIKAWA Hitoshi

  First Department of Medicine, Niigata University School of Medicine

• Tachikawa Hitoshi

  Department Of Cardiology Niigata University School Of Medicine

• WEN Juan

  Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Llfe Sciences

• Wen Juan

  Department Of Clinical Pharmacology Niigata University Of Pharmacy And Applied Llfe Sciences

• Watanabe K

  Cardiovascular Division Tsubame Rosai Hospital

• Watanabe Kenichi

  Division Of Cardiology Tsubame Rosai Hospital

• Aizawa Yoshifusa

  First Department Of Internal Medicine Niigata Universaity School Of Medicine

• Kodama Makoto

  First Dep. Of Medicine Graduate School Of Medical And Dental Sciences Niigata Univ.

• Yamaguchi Kenichi

  Department Of Artificial Complex Systems Engineering Graduate School Of Engineering Hiroshima Univer

• Watanabe Kenichi

  燕労災病院

• Tachikawa Hitoshi

  First Department of Internal Medicine, Niigata University Graduate School of Medical and Dental Sciences

• AIZAWA Yoshifusa

  First Department of Internal Medecine, Niigata University School of Medicine, Niigata, Japan.

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