title: Meloxicam inhibits fipronil-induced apoptosis via modulation of the oxidative stress and inflammatory response in SH-SY5Y cells.
abstract: Oxidative stress and inflammatory responses have been identified as key elements of neuronal cell apoptosis. In this study, we investigated the mechanisms by which inflammatory responses contribute to apoptosis in human neuroblastoma SH-SY5Y cells treated with fipronil (FPN). Based on the cytotoxic mechanism of FPN, we examined the neuroprotective effects of meloxicam against FPN-induced neuronal cell death. Treatment of SH-SY5Y cells with FPN induced apoptosis via activation of caspase-9 and -3, leading to nuclear condensation. In addition, FPN induced oxidative stress and increased expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) via inflammatory stimulation. Pretreatment of cells with meloxicam enhanced the viability of FPN-exposed cells through attenuation of oxidative stress and inflammatory response. FPN activated mitogen activated protein kinase (MAPK) and inhibitors of MAPK abolished FPN-induced COX-2 expression. Meloxicam also attenuated FPN-induced cell death by reducing MAPK-mediated pro-inflammatory factors. Furthermore, we observed both nuclear accumulation of p53 and enhanced levels of cytosolic p53 in a concentration-dependent manner after FPN treatment. Pretreatment of cells with meloxicam blocked the translocation of p53 from the cytosol to the nucleus. Together, these data suggest that meloxicam may exert anti-apoptotic effects against FPN-induced cytotoxicity by both attenuating oxidative stress and inhibiting the inflammatory cascade via inactivation of MAPK and p53 signaling.
authors.affiliation: Department of Pharmacology, College of Medicine, Hanyang University, Korea.|Hanyang Biomedical Research Institute, Seoul, Korea.|Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Pharmacology, College of Medicine, Hanyang University, Korea.|Hanyang Biomedical Research Institute, Seoul, Korea.
authors.forename: Youn Sun
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Agro-food Safety, National Academy of Agricultural Science, Rural Development Administration, Suwon, Korea.
authors.forename: Je-Bong
authors.initials: JB
authors.lastname: Lee
authors.affiliation: Department of Agro-food Safety, National Academy of Agricultural Science, Rural Development Administration, Suwon, Korea.
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Agro-food Safety, National Academy of Agricultural Science, Rural Development Administration, Suwon, Korea.
authors.forename: Min-kyoung
authors.initials: MK
authors.lastname: Paik
authors.affiliation: Department of Agro-food Safety, National Academy of Agricultural Science, Rural Development Administration, Suwon, Korea.
authors.forename: Mihye
authors.initials: M
authors.lastname: Jeong
authors.affiliation: Department of Pharmacology, College of Medicine, Hanyang University, Korea.|Hanyang Biomedical Research Institute, Seoul, Korea.|Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Koh
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D007249:Inflammation / Q000209:etiology; D020935:MAP Kinase Signaling System; D000077239:Meloxicam; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D011720:Pyrazoles / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D011720:Pyrazoles; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D013843:Thiazines; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; C082360:fipronil; D000077239:Meloxicam
keywords: anti-inflammatory; antioxidant; cyclooxygenase-2; fipronil; meloxicam; p53