Deneysel nörodejeneratif hastalık modelinde agomelatinin HT22 hipokampal hücre hattına muhtemel etkisi in vitro model

Neurodegenerative diseases (NDDs) are a series of progressive neuronal deaths due to an antioxidant system imbalance. L glutamic acid (Glu) is a neuroexcitatory transmitter in the nervous system, and excessive extracellular generation induces cell death. Agomelatine (AGO) is an antidepressant drug. This study aims to define the appropriate concentration and dose duration of AGO used as a neuroprotective agent and Glu as a toxic substance on the HT22 cell line. Furthermore, the effect of AGO as a protective agent on HT22 hippocampal cell line against Glu-induced neurotoxicity in vitro model. The MTT assay is used to assess HT22 cell viability. AGO was administered for 24, 48, and 72 hours. The survival rates were expressed as the average percent of cell survival compared to control groups then IC50 values were calculated. After the optimal dose was determined, the experimental groups were divided into nine as: the Blank (complete media), the Cont (complete media+ cell), the Toxic (Glu 5mM), the Treated 1 group ( Glu 5mM+ 30 μM AGO), the Treated 2 group (Glu 5mM+60 μM AGO), the Protection 1 group (30 μM AGO), the Protection 2 group (60 μM AGO), the DMSO 1 group (3μL DMSO), the DMSO 2 group (6μL DMSO). The findings revealed that AGO demonstrated significant inhibitory effects on HT22 cell viability after 24 hours and the effect was significant at 25μM AGO concentration (p ≤ 0.05). Notably, lower AGO concentrations demonstrated a time-dependent increase in inhibitory effects, the data showed that 8 and 2μM significantly reduced the cell viability after 48 and 72 hours (p ≤ 0.001). The IC50 values for AGO were 62.85 μM, 41.86 μM, and 26.65 μM after 24, 48, and 72 hours, respectively. On the other hand, Glu treatment showed significant neurotoxicity, with a 50% reduction in cell viability at 2.465 mM, while higher Glu doses (3, 4, and 5 mM) caused a very high reduction. Combining AGO with Glu treatment effectively suppressed Glu-induced neurotoxicity (p ≤ 0.001). However, caution should be exercised with high concentrations of DMSO, as it exhibited cytotoxicity and had a significant impact compared to the control group. The findings suggest that the neuroprotective effects of AGO in HT22 cells are dose-dependent and influenced by the duration of treatment. It has been observed that low concentrations of AGO exhibit significant protective effects on cell viability. However, moderate to high doses have demonstrated cytotoxicity on cellular viability. Finally; the administration of AGO reduced Glu neurotoxicity and increased cell viability. Keywords: Neurodegenerative diseases; Agomelatine; L-Glutamic Acid; HT22 cell line; MTT