AI Article Synopsis
- Exposure to organic solvents like 1,2-diethylbenzene can lead to health issues such as neurodegenerative diseases and memory impairment due to its toxic metabolite, 1,2-Diacetylbenzene (DAB).
- Prolactin (PRL) is proposed to have neuroprotective effects, and antipsychotic drugs like amisulpride may enhance cognitive performance in Alzheimer's patients through PRL secretion.
- Our study found that amisulpride activates neuroprotective pathways, inhibits DAB-induced inflammation and cell death, suggesting it could be an effective treatment for DAB-related neurotoxicity.
Article Abstract
Exposure to organic solvents is associated with various health problems, including neurodegenerative diseases. Among these solvents, 1,2-diethylbenzene is notable for its ability to produce a toxic metabolite, 1,2-Diacetylbenzene (DAB), which can cause memory impairment. Prolactin (PRL) is theorized to protect the central nervous system. Certain antipsychotic drugs, known for increasing PRL secretion, have shown to improve cognitive performance in psychotic Alzheimer's patients. Among these, amisulpride stands out for its high efficacy, limited side effects, and high selectivity for dopamine D2 receptors. In our study, we explored the potential of amisulpride to inhibit DAB-induced neurotoxicity via PRL activation. Our results show that amisulpride enhances the PRL/JAK/STAT, PI3K/AKT, and BDNF/ERK/CREB pathways, playing critical roles in PRL's neuroprotection pathways and memory formation. Additionally, amisulpride inhibited DAB-triggered NLRP3 inflammasome activation and apoptosis. Collectively, these findings suggest that amisulpride may be a promising therapeutic intervention for DAB-induced neurotoxicity, partly through activating the PRL pathway.
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| http://dx.doi.org/10.1016/j.etap.2024.104418 | DOI Listing |
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Article Synopsis
- Exposure to organic solvents like 1,2-diethylbenzene can lead to health issues such as neurodegenerative diseases and memory impairment due to its toxic metabolite, 1,2-Diacetylbenzene (DAB).
- Prolactin (PRL) is proposed to have neuroprotective effects, and antipsychotic drugs like amisulpride may enhance cognitive performance in Alzheimer's patients through PRL secretion.
- Our study found that amisulpride activates neuroprotective pathways, inhibits DAB-induced inflammation and cell death, suggesting it could be an effective treatment for DAB-related neurotoxicity.
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1,2-diacetylbenzene (1,2-DAB) is a neurotoxic component of aromatic solvents commonly used in industrial applications that induces neuropathological changes in animals. This study unraveled the toxic impact of 1,2-DAB in nerve tissues, explant cultures, and neuron-glial cultures, and explored whether herbal products can mitigate its toxicity. The effects of DAB on axonal transport were studied in retinal explant cultures grown in a micro-patterned dish.
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Environmental substances or metabolites induce neuronal damage through oxidative stress. Environmental organic solvent metabolite, 1,2-diacetylbenzene (1,2-DAB), treated rats develop limb weakness with neuropathological damage in both the central and peripheral nervous systems. In this experiment, we examined the relevance of 1,2-DAB-induced toxicity to increased oxidative stress using human dopaminergic neuroblastoma SHSY5Y cells.
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