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To investigate the potential role of ferroptosis in the neurotoxicity induced by deltamethrin (DM) exposure.
Mice hippocampal neuronal cells HT22 cells were treated with DM at different doses (1, 2, 5, 10, 20, 50, 100, 200, and 400 μmol/L) for 24 h, cell survival rate was detected by MTT method to determine the optimal dose (2, 10, and 50 μmol/L). The cell morphology was observed by microscope. The level of lipid peroxidation was detected by flow cytometry. The level of glutathione (GSH) and the content of ferrous ion (Fe2+) were detected by the kit. The levels of ferritin heavy chain (FTH), light chain (FTL) protein and glutathione peroxidase 4 (GPX4) were detected by Western Blotting.
With the increase of DM dose, the number of HT22 cells gradually decreased, the morphology changed and the tentacles antennae broke. Compared with the control group, the survival rate of DM infected groups were significantly decreased (F=349.8, P<0.01), and the level of intracellular lipid peroxidation was significantly increased (F=14.86, P<0.01). With the increase of dose, GSH level in HT22 cells in 2, 10 and 50 μmol/L DM groups was significantly lower than that in control group (F=11.56, P<0.01), and Fe2+ level in 10 and 50 μmol/L DM groups was significantly higher than that in control group (F=17.67, P<0.01). Compared with the control group, GPX4 and FTL protein expressions in the 50 μmol/L DM group were significantly decreased with the increase of dose (FGPX4=3.313, P<0.05; FFTL=2.003, P<0.05), and FTH protein expressions in the 2, 10, 50 μmol/L DM groups were significantly increased with the increase of dose (F=16.95, P<0.01). Pretreatment with Fer-1, an ferroptosis inhibitor, for 2 h significantly reversed GSH, lipid peroxidation and Fe2+ levels in 50 μmol/L DM group (FGSH=215.5, P<0.01; Flipid p eroxide=17.97, P<0.01; FFe2+=23.26, P<0.01).
DM exposure induces ferroptosis in HT22 cells of mice hippocampal neurons leading to neurotoxicity, the mechanism of which may be related to intracellular lipid peroxidation and iron metabolism disorder.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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