P2.15. EVALUATION OF NEUROPROTECTIVE POTENTIAL OF CLASSICAL AND NOVEL ANTI-INFLAMMATORY COMPOUNDS FOR PARKINSON’S DISEASE – IN VITRO STUDY IN HUMAN NEUROBLASTOMA SH-SY5Y CELLS
Danuta Jantas1, Aleksandra Mąsior1, Piotr Chmielarz1, Ryszard Bugno2, Grzegorz Kreiner1
1 Maj Institute of Pharmacology Polish Academy of Sciences, Department of Brain Biochemistry, Smętna 12 Str, 31-343 Kraków, Poland
2 Maj Institute of Pharmacology Polish Academy of Sciences, Department of Medicinal Chemistry, Smętna 12 Str, 31-343 Kraków, Poland
INTRODUCTION: MIP001 is novel anti-inflammatory and analgesic drug with favourable safety profile even at high doses.
AIM(S): Since neuroinflammation is a significant contributor to pathogenesis of various neurodegenerative diseases, in this study we screened for potential neuroprotective effect of MIP001 in cellular models of Parkinson’s disease.
METHOD(S): We compared the effectiveness of MIP001 (1-300 microM) with clinically used anti-inflammatory drug, ibuprofen (Ibu, 10-300 microM) against cell damage induced by hydrogen peroxide (H2O2), 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium ion (MPP+) in undifferentiated (UN-) and retinoic acid (RA-) differentiated human neuroblastoma SH-SY5Y cells. The neuroprotective effects were measured by biochemical assays at the level of cell viability (MTT reduction test) and cytotoxicity (LDH release test).
RESULTS: We demonstrated that MIP001 and Ibu at concentrations up to 100 microM when given for 24 and 48 hours did not evoke any detrimental effects in UN- and RA-SH-SY5Y cell viability. MIP001 at concentrations of 10-100 microM significantly attenuated the cytotoxic effect of MPP+ in UN- and RA-SH-SY5Y cells, whereas it was only slightly protective at concentration of 30 microM against the 6-OHDA evoked damage in UN-SH-SY5Y, and against H2O2-evoked cell death in RA-SH-SY5Y cells. We did not notice any protection mediated by Ibu in all tested cell damage models in both studied SH-SY5Y cell phenotypes.
CONCLUSIONS: Our results evidenced a neuroprotective potential of MIP001 against various cell damaging factors, with its higher effectiveness in apoptotic (MPP+), than oxidative stress-based (H2O2 and 6-OHDA) neuronal cell damage models. Thus it is highly reasonable to further investigate MIP001 neuroprotective potency in other cellular and animal models of PD.
FINANCIAL SUPPORT: The study was supported by a programme coordinated by the Medical Research Agency, co-financed by the European Union under the NextGeneration EU initiative, within the framework of the National Recovery Plan, Component D, Investment D3.1.1 (project no. 2024/ABM/03/KPO/KPOD.07.07-IW.07-0173/24-00).