香芹酚通过调节NRF-2/HO-1/NF-κB的表达减轻氯化汞诱导的神经毒性

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology Pub Date : 2025-08-09 DOI:10.1016/j.jtemb.2025.127715

Nurhan Akaras , Hasan Şimşek , Mustafa İleritürk , Sefa Küçükler , Cihan Gür , Fatih Mehmet Kandemir

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引用次数: 0

摘要

氯化汞（HgCl2）是一种对中枢神经系统具有严重毒性作用的环境污染物。香芹酚（CRV）具有植物治疗、药理、生物学和芳香特性，具有神经保护作用。本研究的目的是探讨CRV对hgcl2诱导的大鼠中枢神经毒性可能的神经保护作用。在研究中，给大鼠单独或联合给药HgCl2（1.23 mg/kg）和CRV(25或50 mg/kg) 7天。然后，采用生化、分子、组织学和免疫组织化学方法分析脑组织自噬、凋亡、炎症和氧化应激过程的特异性蛋白和病理变化。结果表明，CRV处理显著提高了抗氧化酶（过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶）活性和非酶（谷胱甘肽）抗氧化剂活性，同时降低了hgcl2诱导的脂质过氧化。此外，我们还确定了CRV给药后氧化应激参数Nrf-2、HO-1、NQO1 mRNA转录水平升高。结果显示，HgCl2可提高NF-κB、TNF-α、IL-1β、iNOS和nNOS细胞因子以及Rage、STAT3、NLRP3、MAPK14、MAPK15和JNK的表达，而CRV可抑制这些基因的表达。本研究确定HgCl2可诱导凋亡（caspase-3、Bax、Bcl-2）和自噬（Beclin-1）标志物，而CRV可通过抗凋亡和抗自噬来保护脑组织免受HgCl2的破坏作用。此外，给予CRV后，hgcl2诱导的脑组织中Akt-2和Foxo1表达降低，GFAP水平升高。H&；E染色结果显示，CRV保留了大脑皮层的组织结构和完整性。本研究结果表明，CRV通过减少氧化应激、炎症、细胞凋亡和自噬，对hgcl2诱导的神经毒性具有神经预防潜力。

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Carvacrol mitigates Mercury chloride induced neurotoxicity by regulation of NRF-2/HO-1/NF-κB expression

Mercury chloride (HgCl2) is an environmental pollutant that has serious toxic effects on the central nervous system. Carvacrol (CRV), which has phytotherapeutic, pharmacological, biological, and aromatic properties, has neuroprotective effects. The aim of this study was to investigate the possible neuroprotective effect of CRV on HgCl2-induced central neurotoxicity in rats.

In the study, HgCl₂ (1.23 mg/kg) and CRV (25 or 50 mg/kg) alone or their combinations were administered to rats for 7 days. Then, the proteins and pathological changes specific to autophagy, apoptosis, inflammation and oxidative stress processes in the brain tissue were analyzed by biochemical, molecular, histological and immunohistochemical methods. It was determined that CRV treatment significantly increased antioxidant enzyme (catalase, superoxide dismutase and glutathione peroxidase) activities and non-enzymatic (glutathione) antioxidants while reducing HgCl₂-induced lipid peroxidation. In addition, it was determined that Nrf-2, HO-1, NQO1 mRNA transcript levels, which are among the oxidative stress parameters of CRV administration, increased. It was observed that HgCl₂ increased the expression of NF-κB, TNF-α, IL-1β, iNOS and nNOS cytokines and Rage, STAT3, NLRP3, MAPK14, MAPK15 and JNK, whereas CRV treatment suppressed these genes. In this study, it was determined that HgCl₂ induces apoptotic (caspase-3, Bax, Bcl-2) and autophagic (Beclin-1) markers, whereas CRV can protect brain tissues from the destructive effect of H HgCl₂ by showing anti-apoptotic and anti-autophagic. In addition, decreased Akt-2 and Foxo1 expression and increased GFAP levels in HgCl₂-induced brain tissue were regulated after CRV administration. The H&E staining results showed that CRV preserved the histological architecture and integrity of the cerebral cortex.

The findings of this study indicate that CRV has neuropreventive potential against HgCl₂-induced neurotoxicity by reducing oxidative stress, inflammation, apoptosis and autophagy.

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来源期刊

Journal of Trace Elements in Medicine and Biology 医学-内分泌学与代谢

CiteScore

6.60

自引率

2.90%

发文量

202

审稿时长

85 days

期刊介绍： The journal provides the reader with a thorough description of theoretical and applied aspects of trace elements in medicine and biology and is devoted to the advancement of scientific knowledge about trace elements and trace element species. Trace elements play essential roles in the maintenance of physiological processes. During the last decades there has been a great deal of scientific investigation about the function and binding of trace elements. The Journal of Trace Elements in Medicine and Biology focuses on the description and dissemination of scientific results concerning the role of trace elements with respect to their mode of action in health and disease and nutritional importance. Progress in the knowledge of the biological role of trace elements depends, however, on advances in trace elements chemistry. Thus the Journal of Trace Elements in Medicine and Biology will include only those papers that base their results on proven analytical methods. Also, we only publish those articles in which the quality assurance regarding the execution of experiments and achievement of results is guaranteed.