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丁香酚对百草枯改变的Wistar大鼠小脑SNCA/LZTS3/MAPT的调节作用

Regulatory roles of eugenol in paraquat-altered SNCA/LZTS3/MAPT in the cerebellum of Wistar rats.

作者信息

Uchewa Obinna Onwe, Ibegbu Augustine Oseloka, Okafor Samuel Okoronkwo, Nwafor Joseph Alo, Egwu Ogugua Augustine

机构信息

Anatomy Department, Faculty of Basic Medical Sciences, Alex Ekwueme, Federal University, Ndufu-Alike, Ebonyi State, Nigeria.

Anatomy Department, Faculty of Basic Medical Sciences, David Umahi Federal University of Health Sciences, Uburu, Ebonyi State, Nigeria.

出版信息

Lab Anim Res. 2025 Jan 15;41(1):2. doi: 10.1186/s42826-025-00236-8.

Abstract

BACKGROUND

The Microtubules-associated protein tau (MAPT), alpha-synuclein (SNCA), and leucine zipper tumor suppressor 3 (LZTS3) genes are implicated in neurodegeneration and tumor suppression, respectively. This study investigated the regulatory roles of eugenol on paraquat-altered genes.

RESULTS

Forty male Wistar rats divided into five groups of eight rats were used. The control group received normal saline; the Paraquat (PQ)-untreated group received only Paraquat. The low dose of eugenol was 200 mg/kg, the medium dose of eugenol was 400 mg/kg, and the high dose of eugenol was 600 mg/kg. All groups except the control group received 10 mg/kg of PQ orally for 14 days at one-day intervals, allowing PQ in the rats for 28 days. Eugenol treatment started on the 29th and lasted 14 days. Motor impairments were determined using wire string and beam-walk; biomarkers were estimated using cerebellar homogenates, while frozen cerebellum was used to study LZTS3, MAPT, and SNCA gene expression. LZTS3 was significantly suppressed in the PQ-untreated group and highly expressed in the eugenol-treated group. The MAPT and SNCA genes were overexpressed in the PQ-untreated group compared to the control group. Eugenol significantly decreased the expression of these genes compared to that in the PQ-untreated group. Antioxidants were reduced considerably, and oxidative stress markers were increased significantly, which could have caused increased protein fibrillation and reduced limb functionality. Histology revealed that eugenol mitigated the alterations caused by Paraquat.

CONCLUSIONS

PQ can enhance tumor expression in addition to causing neurotoxicity, which decreases limb functionality, while eugenol, an antioxidant, can mitigate the effects of PQ.

摘要

背景

微管相关蛋白tau(MAPT)、α-突触核蛋白(SNCA)和亮氨酸拉链肿瘤抑制因子3(LZTS3)基因分别与神经退行性变和肿瘤抑制有关。本研究调查了丁香酚对百草枯改变的基因的调节作用。

结果

使用40只雄性Wistar大鼠,分为五组,每组8只。对照组给予生理盐水;百草枯(PQ)未处理组仅给予百草枯。丁香酚低剂量为200mg/kg,中剂量为400mg/kg,高剂量为600mg/kg。除对照组外,所有组均每隔一天口服10mg/kg的PQ,持续14天,使大鼠体内的PQ作用28天。丁香酚治疗从第29天开始,持续14天。使用钢丝串和横梁行走试验测定运动障碍;使用小脑匀浆估计生物标志物,同时使用冷冻小脑研究LZTS3、MAPT和SNCA基因表达。LZTS3在PQ未处理组中显著受抑制,在丁香酚处理组中高表达。与对照组相比,MAPT和SNCA基因在PQ未处理组中过表达。与PQ未处理组相比,丁香酚显著降低了这些基因的表达。抗氧化剂显著减少,氧化应激标志物显著增加,这可能导致蛋白质纤维化增加和肢体功能降低。组织学显示丁香酚减轻了百草枯引起的改变。

结论

PQ除了引起神经毒性导致肢体功能降低外,还可增强肿瘤表达,而抗氧化剂丁香酚可减轻PQ的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a10/11734554/153214e1d68d/42826_2025_236_Fig1_HTML.jpg

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