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Meloxicam inhibits fipronil-induced apoptosis via modulation of the oxidative stress and inflammatory response in SH-SY5Y cells.
J Appl Toxicol. 2016 Jan; 36(1):10-23.JA

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+Show Affiliations

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.Department of Pharmacology, College of Medicine, Hanyang University, Korea. Hanyang Biomedical Research Institute, Seoul, Korea.Department of Agro-food Safety, National Academy of Agricultural Science, Rural Development Administration, Suwon, Korea.Department of Agro-food Safety, National Academy of Agricultural Science, Rural Development Administration, Suwon, Korea.Department of Agro-food Safety, National Academy of Agricultural Science, Rural Development Administration, Suwon, Korea.Department of Agro-food Safety, National Academy of Agricultural Science, Rural Development Administration, Suwon, Korea.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25772694

Citation

Park, Jae Hyeon, et al. "Meloxicam Inhibits Fipronil-induced Apoptosis Via Modulation of the Oxidative Stress and Inflammatory Response in SH-SY5Y Cells." Journal of Applied Toxicology : JAT, vol. 36, no. 1, 2016, pp. 10-23.
Park JH, Park YS, Lee JB, et al. Meloxicam inhibits fipronil-induced apoptosis via modulation of the oxidative stress and inflammatory response in SH-SY5Y cells. J Appl Toxicol. 2016;36(1):10-23.
Park, J. H., Park, Y. S., Lee, J. B., Park, K. H., Paik, M. K., Jeong, M., & Koh, H. C. (2016). Meloxicam inhibits fipronil-induced apoptosis via modulation of the oxidative stress and inflammatory response in SH-SY5Y cells. Journal of Applied Toxicology : JAT, 36(1), 10-23. https://doi.org/10.1002/jat.3136
Park JH, et al. Meloxicam Inhibits Fipronil-induced Apoptosis Via Modulation of the Oxidative Stress and Inflammatory Response in SH-SY5Y Cells. J Appl Toxicol. 2016;36(1):10-23. PubMed PMID: 25772694.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Meloxicam inhibits fipronil-induced apoptosis via modulation of the oxidative stress and inflammatory response in SH-SY5Y cells. AU - Park,Jae Hyeon, AU - Park,Youn Sun, AU - Lee,Je-Bong, AU - Park,Kyung-Hun, AU - Paik,Min-kyoung, AU - Jeong,Mihye, AU - Koh,Hyun Chul, Y1 - 2015/03/13/ PY - 2014/12/09/received PY - 2015/01/05/revised PY - 2015/01/26/accepted PY - 2015/3/17/entrez PY - 2015/3/17/pubmed PY - 2016/9/27/medline KW - anti-inflammatory KW - antioxidant KW - cyclooxygenase-2 KW - fipronil KW - meloxicam KW - p53 SP - 10 EP - 23 JF - Journal of applied toxicology : JAT JO - J Appl Toxicol VL - 36 IS - 1 N2 - 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. SN - 1099-1263 UR - https://www.unboundmedicine.com/medline/citation/25772694/Meloxicam_inhibits_fipronil_induced_apoptosis_via_modulation_of_the_oxidative_stress_and_inflammatory_response_in_SH_SY5Y_cells_ L2 - https://doi.org/10.1002/jat.3136 DB - PRIME DP - Unbound Medicine ER -