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 -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.

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