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.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Apoptosis/drug effects , Oxidative Stress/drug effects , Pyrazoles/antagonists & inhibitors , Thiazines/pharmacology , Thiazoles/pharmacology , Antioxidants/pharmacology , Cell Line, Tumor , Humans , Inflammation/etiology , MAP Kinase Signaling System , Meloxicam , Mitochondria/drug effects , Mitochondria/physiology , Pyrazoles/pharmacology , Reactive Oxygen Species/metabolism , Tumor Suppressor Protein p53/physiologyABSTRACT
To implement the globally harmonized system of classification and labelling of chemicals (GHS) in Korea, an inter-ministerial GHS committee, involving 8 ministries and an expert working group composed of 9 experts from relevant organizations and one private consultant, have made some progress towards implementation by 2008. As such, the first revision of the official Korean translated version of the GHS in accordance with the GHS purple book revision 1 in 2005, including annexes, started in August, 2006, was completed in December, 2006. The Ministry of Labor also finally revised the Industrial Safety and Health Act (ISHA) relating to the GHS and the detailed notification was announced on Dec 12, 2006 and became effective immediately. The revised ISHA will allow continued use of the existing hazard communication system until Jun 30, 2008. Other revisions of chemical-related regulations will follow soon to facilitate the implementation of the GHS by 2008. Besides, inter-ministerial collaborative efforts on harmonizing regulations and disseminating the GHS in Korea will continue to avoid any confusion or duplication and for the effective use of resources.
