Celecoxib, indomethacin and ibuprofen prevent 6-hydroxydopamine-induced PC12 cell death through the inhibition of NFκB and SAPK/JNK pathways

Document Type: Original Article


1 Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

2 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran


Objective(s): The possible action of nonsteroidal anti-inflammatory drugs (NSAIDs) in the reduction of reactive oxygen species (ROS) and also as anti-apoptotic agents may suggest them as putative agents for the treatment of neurodegenerative diseases. This study was designed to explore some pathways alterations induced by NSAIDs following 6-hydroxydopamine (6-OHDA)-induced cell death in PC12 cells as an in vitro model of Parkinson's disease (PD) and to compare the effects of celecoxib, indomethacin and ibuprofen.
Materials and Methods: The cell viability, ROS content, glutathione (GSH) level, and apoptosis were measured using resazurin, dichlorofluorescein diacetate (DCFH-DA), 5,5′-dithiobis-2-nitrobenzoic acid (DTNB), propidium iodide (PI) and flowcytometry, real-time PCR and western blot.
Results: Based on the results, pretreatment with celecoxib, indomethacin and ibuprofen for 24 hr significantly induced concentration and time-dependent protection against 6-OHDA-induced PC12 cell death. Cell viability (P<0.001), GSH level (P<0.01) and cytoplasmic content of nuclear factor kappa B (NFκB) (P<0.01) were increased, also ROS content (P<0.001) and apoptosis biomarkers such as the cleaved caspase-3 (P<0.001), Bax (P<0.01), phospho- stress-activated protein kinases / c-Jun N-terminal kinases (P-SPAK/JNK) (P<0.01) and cleaved poly ADP ribose polymerase (PARP) (P<0.001) protein levels were all decreased after pretreatment of cells with NSAIDs in 6-OHDA-induced PC12 cells.
Conclusion: It is suggested that NFκB and SAPK/JNK pathways have an important role in 6-OHDA-induced cell injury. Overall, it seems that pretreatment with NSAIDs protect dopaminergic cells and may have the potential to slow the progression of PD.


Main Subjects

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