title: Neuroprotective effect of triflusal and its main metabolite, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB), in the postischemic brain.
abstract: 2-Hydroxy-4-trifluoromethylbenzoic acid (HTB) is a metabolite of triflusal (TF), and has been reported to exert anti-inflammatory effect. In this study, the authors investigated whether HTB has a neuroprotective effect against ischemic brain injuries. We showed that intravenous administration of HTB (5mg/kg) 30min before or 1, 3, or 6h after middle cerebral artery occlusion (MCAO) reduced brain infarct to 10.4±3.3%, 16.9±2.3%, 22.2±1.5% and 40.7±7.5%, respectively, of that of treatment-naive MCAO controls, and the therapeutic time window extended to 9h after MCAO (40.7±7.5%). Furthermore, HTB suppressed infarct formation, protected motor activities, and ameliorated neurological deficits more effectively than by TF or salicylic acid (SA). HTB markedly suppressed microglial activation and proinflammatory cytokines expressions in the postischemic brain and in BV2 cells and suppressed LPS-induced nitrite production by inhibiting IkB degradation. In addition, HTB suppressed NMDA-induced neuronal cell death more effectively than TF or SA in primary cortical neuron cultures. Together, these results indicate that HTB has multi-modal protective effects against ischemic brain damage that encompass anti-inflammatory, anti-excitotoxicity, and anti-Zn2+-toxicity effects.
authors.affiliation: Department of Biomedical Sciences, Inha University School of Medicine, Republic of Korea; Medical Research Center, Inha University School of Medicine, Republic of Korea.
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Medical Research Center, Inha University School of Medicine, Republic of Korea; Department of Anatomy, Inha University School of Medicine, Inchon, Republic of Korea.
authors.forename: Kyu-Jin
authors.initials: KJ
authors.lastname: Choi
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Sung-Hwa
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: Medical Research Center, Inha University School of Medicine, Republic of Korea; Department of Anatomy, Inha University School of Medicine, Inchon, Republic of Korea. Electronic address: jklee@inha.ac.kr.
authors.forename: Ja-Kyeong
authors.initials: JK
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018696:Neuroprotective Agents; D012459:Salicylates; C016167:triflusal; C033502:4-trifluoromethylsalicylic acid; D001241:Aspirin
keywords: Anti-inflammation; HTB; MCAO; Neuroprotection; Triflusal