抑制可溶性环氧化物水解酶可减少百草枯在啮齿动物中的神经毒性。
Inhibition of soluble epoxide hydrolase reduces paraquat neurotoxicity in rodents.
机构信息
Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA 95616, USA.
Department of Nutrition, University of California Davis, Davis, CA 95616, USA.
出版信息
Environ Toxicol Pharmacol. 2023 Mar;98:104070. doi: 10.1016/j.etap.2023.104070. Epub 2023 Jan 20.
Given the paucity of research surrounding the effect of chronic paraquat on striatal neurotoxicity, there is a need for further investigation into the neurotoxic effects of paraquat in mouse striatum. Furthermore, while previous studies have shown that inhibiting soluble epoxide hydrolase mitigates MPTP-mediated endoplasmic reticulum stress in mouse striatum, its effect on paraquat toxicity is still unknown. Thus, this study attempts to observe changes in inflammatory and endoplasmic reticulum stress markers in mouse striatum following chronic paraquat administration to determine whether inhibiting soluble epoxide hydrolase mitigates paraquat-induced neurotoxicity and whether it can reduce TLR4-mediated inflammation in primary astrocytes and microglia. Our results show that while the pro-inflammatory effect of chronic paraquat is small, there is a significant induction of inflammatory and cellular stress markers, such as COX2 and CHOP, that can be mitigated through a prophylactic administration of a soluble epoxide hydrolase inhibitor.
鉴于慢性百草枯对纹状体神经毒性影响的研究甚少，因此需要进一步研究百草枯对小鼠纹状体的神经毒性作用。此外，虽然先前的研究表明，抑制可溶性环氧化物水解酶可减轻 MPTP 介导的小鼠纹状体内质网应激，但它对百草枯毒性的影响尚不清楚。因此，本研究试图观察慢性百草枯给药后小鼠纹状体中炎症和内质网应激标志物的变化，以确定抑制可溶性环氧化物水解酶是否可以减轻百草枯诱导的神经毒性，以及是否可以减少 TLR4 介导的原代星形胶质细胞和小胶质细胞炎症。我们的结果表明，虽然慢性百草枯的促炎作用较小，但炎症和细胞应激标志物，如 COX2 和 CHOP 的表达显著增加，而通过预防性给予可溶性环氧化物水解酶抑制剂可减轻这种增加。
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