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    Effects of L-dopa and p-coumaric acid combination on oxidative stress, DNA damage, and mitochondrial apoptosis in neuroblastoma cells
    (Bangladesh Pharmacological Soc, 2023) Turker, Nebiye Pelin; Bakar, Elvan
    This study aimed to investigate the effects of levodopa (L-dopa), p-coumaric acid, and combinations in the neuroblastoma (N1E-115) cell. L-dopa and L-dopa plus p-coumaric acid group caused oxidative stress by increasing 12.5 and 3.7-fold in superoxide dismutase gene, 11.5 and 4.8-fold increase in catalase gene, respectively. In L-dopa and L-dopa plus p-coumaric acid application, p21 gene expression increased 1.3-fold and 3.2-fold, and the cell cycle stopped in the G1 phase in response to stress in the treatment groups. In the application of L-dopa plus p-coumaric acid to N1E-115 cells, the BCL-2 gene, which is an apoptosis inhibitor, was suppressed and the BAX gene increased 13-fold compared to the control. As a result, it was determined that the cytotoxic effect of L-dopa plus p-coumaric acid application was less than the individual application of the substances, and p-coumaric acid had an inhibitory effect on L-dopa-induced stress.
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    In vitro hepatotoxicity evaluation of methotrexate-loaded niosome formulation: fabrication, characterization and cell culture studies
    (Tubitak Scientific & Technological Research Council Turkey, 2023) Ergin, Ahmet Dogan; Oltulu, Cagatay; Turker, Nebiye Pelin; Demirbolat, Gulen Melike
    Background/aim: Methotrexate (MTX) is a folic acid antagonist that is widely used to treat osteosarcoma, leukemia, breast cancer, and autoimmune and inflammatory diseases. The most important concerns with MTX are its poor solubility and high toxicity, particularly in liver cells. To enhance its solubility and to minimize its toxicity, we encapsulated MTX in niosomes and investigated its hepatotoxicity mechanisms using genetic biomarkers. Materials and methods: Niosomes were successfully prepared using a modified thin film method, and the prepared monodisperse smallsized formulation was subsequently characterized. In vitro cytotoxicity studies were performed both in hepatocarcinoma (HEP3G) and healthy liver (AML12) cell lines. Specifically, immunofluorescence assay and evaluation of the expression levels of apoptotic, antioxidant, heat shock protein, and oxidative stress genes were performed. Results: The formulation had a particle size of 117.1 +/- 33 nm, a surface charge of -38.41 +/- 0.7 mV, and an encapsulation efficiency of 59.7% +/- 2.3%. The results showed that the niosomal formulation exhibited significantly higher cytotoxic effects in HEP3G than in AML12. The immunofluorescence and genetic analyses showed that the increased cytotoxicity of niosomes resulted mainly from oxidative stress and slight apoptosis. Conclusion: These results demonstrated that niosomal drug delivery systems could be a new potential formulation for minimizing MTX-related hepatotoxicity.