Akaras Nurhan, Şimşek Hasan, İleritürk Mustafa, Küçükler Sefa, Gür Cihan, Kandemir Fatih Mehmet
Department of Histology and Embryology, Faculty of Medicine, Aksaray University, Aksaray, Turkey.
Department of Physiology, Faculty of Medicine, Aksaray University, Aksaray, Turkey.
J Trace Elem Med Biol. 2025 Oct;91:127715. doi: 10.1016/j.jtemb.2025.127715. Epub 2025 Aug 9.
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, HgCl (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 HgCl-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 HgCl 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 HgCl induces apoptotic (caspase-3, Bax, Bcl-2) and autophagic (Beclin-1) markers, whereas CRV can protect brain tissues from the destructive effect of H HgCl by showing anti-apoptotic and anti-autophagic. In addition, decreased Akt-2 and Foxo1 expression and increased GFAP levels in HgCl-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 HgCl-induced neurotoxicity by reducing oxidative stress, inflammation, apoptosis and autophagy.
氯化汞（HgCl₂）是一种环境污染物，对中枢神经系统具有严重的毒性作用。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的可能神经保护作用。在该研究中，将HgCl（1.23 mg/kg）和CRV（25或50 mg/kg）单独或联合给予大鼠7天。然后，通过生化、分子、组织学和免疫组织化学方法分析脑组织中自噬、凋亡、炎症和氧化应激过程特有的蛋白质和病理变化。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）抗氧化剂水平，同时降低了HgCl诱导的脂质过氧化。此外，还发现CRV给药后，作为氧化应激参数之一的Nrf-2、HO-1、NQO1 mRNA转录水平升高。观察到HgCl增加了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处理抑制了这些基因。在本研究中，确定HgCl诱导凋亡（半胱天冬酶-3、Bax、Bcl-2）和自噬（Beclin-1）标志物，而CRV可通过显示抗凋亡和抗自噬作用保护脑组织免受HgCl的破坏作用。此外，CRV给药后，HgCl诱导的脑组织中Akt-2和Foxo1表达降低以及GFAP水平升高得到调节。苏木精-伊红染色结果表明，CRV保留了大脑皮质的组织结构和完整性。本研究结果表明，CRV通过降低氧化应激、炎症、凋亡和自噬，对HgCl诱导的神经毒性具有神经预防潜力。
