Saeed Saira, Saleem Ammara, Khan Muhammad Imran, Akhtar Kanwal, Khan Aslam, Akhtar Muhammad Furqan, Bouallegue Amir, Bourhia Mohammed, Kadasah Sultan F
Riphah Institute of Pharmaceutical Sciences, Riphah International University Lahore, Lahore, Pakistan.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Aug 30. doi: 10.1007/s00210-025-04514-z.
The aim of this investigation was to explore the potential effects of veratric acid on central nervous and reproductive toxicity caused by mercuric chloride in female rats. Six mercury-exposed female rats in each group were separately treated with 12.5, 25, and 50 mg/kg of veratric acid. The brain and ovaries were then evaluated for biochemical and histopathological analysis. Based on the results obtained through this study's assessment methods, mercuric chloride (HgCl) administration may harm the central nervous and reproductive systems in females. Evidence suggested that test subjects experienced increased apoptosis, indicated by higher levels of caspase-3, hormonal imbalances with results indicating significantly increased levels of estrogen, and non-significant increased FSH and decreased values of LH, alongside increased levels of inflammation markers such as significantly lower values of NF-κB and oxidative stress levels indicated by significantly higher levels of MDA. In addition to these physiological changes, behavioral impairments in the Rotarod test, and the activity cage test also emerged among rats, as well as notable alternations and the presence of inflammatory cells in histopathology analyses appeared. The administration of veratric acid at different doses was observed to mitigate mercuric chloride toxic effects, as evidenced by improvements in hormonal profile as it caused estrogen, FSH, and testosterone levels to decrease significantly; oxidative stress also improved, evidenced from reduced levels of MDA and increased levels of GSH. Veratric acid also improved the behavioral activities of rats, as motor coordination is improved in the Rotarod test and improvement in the activity cage test. This study also revealed the positive effect of veratric acid on apoptosis, as results indicated a reduced levels (p < 0.001) of caspase-3. Studies with data revealed that veratric acid can shield female rats from detrimental mercuric chloride-induced toxicity. Considering this evidence in exploring the drug's ability to counteract such toxicity would prove to be a constructive option for forthcoming investigations.
本研究的目的是探讨藜芦酸对氯化汞所致雌性大鼠中枢神经和生殖毒性的潜在影响。每组6只汞暴露雌性大鼠分别给予12.5、25和50mg/kg的藜芦酸。然后对大脑和卵巢进行生化和组织病理学分析。根据本研究评估方法获得的结果,氯化汞给药可能会损害雌性大鼠的中枢神经和生殖系统。有证据表明,受试对象的细胞凋亡增加,表现为半胱天冬酶-3水平升高;激素失衡,结果表明雌激素水平显著升高,促卵泡激素升高不显著,促黄体生成素值降低,同时炎症标志物水平升高,如核因子-κB值显著降低,丙二醛水平显著升高表明氧化应激水平升高。除了这些生理变化外,大鼠在转棒试验和活动笼试验中还出现了行为障碍,组织病理学分析中也出现了明显的改变和炎症细胞。观察到不同剂量的藜芦酸给药可减轻氯化汞的毒性作用,这表现为激素水平的改善,因为它使雌激素、促卵泡激素和睾酮水平显著降低;氧化应激也得到改善,表现为丙二醛水平降低和谷胱甘肽水平升高。藜芦酸还改善了大鼠的行为活动,因为在转棒试验中运动协调性得到改善,在活动笼试验中也有所改善。本研究还揭示了藜芦酸对细胞凋亡的积极作用,结果表明半胱天冬酶-3水平降低(p<0.001)。有数据的研究表明,藜芦酸可以保护雌性大鼠免受氯化汞诱导的有害毒性。考虑到这些证据,探索该药物对抗此类毒性的能力将是未来研究的一个建设性选择。