Protective Effects of Trimetazidine Against Bilirubin-Induced Neurotoxicity

Background and aims: We aimed to research the effects of limiting oxidation and blocking membrane calcium channels on induced-bilirubin neurotoxicity. For this purpose, we used anti-ischemic drugs that Trimetazidine (TMZ) has features as limiting membrane damage induced by reactive oxygen radicals and decreasing overload calcium into the cell. Methods: In this study, the SH-SY5Y neuroblastoma cell line was used. Cells at a concentration of 3x104 cell/100μl were seeded to a 96-well plate. The toxic doses of bilirubin and the protecting effect of TMZ were determined by the MTT test. To detect the poisonous mechanism of bilirubin, the Muse Cell Analyzer Annexin V&Dead Cell assay kit protocol was applied. Determination of the intracellular free oxygen radicals was made with the flow cytometric oxidative stress assay according to the Muse Cell Analyzer Oxidative Stress assay protocols. Results: 10 and 100 μM doses of bilirubin were determined as toxic, while for TMZ, 10 and 100 μM treatments were determined as protective doses. In both doses of TMZ, we observed significant positive effects against oxidative stress and apoptosis caused by 10 μM bilirubin. Conclusion: Trimetazidine should be further studied as a potential protecting molecule in hyperbilirubinemia.