Türkez Hasan, Özdemir Tozlu Özlem, Saraçoğlu Melik, Yıldız Edanur, Baba Cem, Bayram Cemil, Çınar Burak, Yıldırım Serkan, Kılıçlıoğlu Metin, Gözegir Berrah, Çadırcı Kenan
Department of Medical Biology, Faculty of Medicine, Atatürk University, Erzurum, Turkey.
Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum, Turkey.
Regul Toxicol Pharmacol. 2025 May 3;161:105840. doi: 10.1016/j.yrtph.2025.105840.
Colemanite (COL), a boron-containing mineral, has shown potential therapeutic applications, particularly in the fields of drug delivery and bone health. However, despite its promising bioactive properties, there is a lack of comprehensive toxicological data on its safety, especially regarding its potential medical use. Previous studies have primarily focused on its industrial applications, with limited investigation into its biological effects. This gap in knowledge prompted the current study, which aimed to investigate the subacute toxicity of colemanite in rats using behavioral, hematological, biochemical, genotoxic, and histopathological analyses. Over a 7-day period, rats were treated with doses of 10, 30, and 300 mg/kg. Behavioral assessments, including locomotor activity and elevated plus maze tests, indicated enhanced exploratory behaviors, indicating heightened curiosity or activity and no alterations in motor coordination or anxiety-like behaviors. Hematological findings revealed dose-dependent reductions in hematocrit, hemoglobin, and red blood cell counts, while biochemical analyses showed elevated aspartate aminotransferase, lactate dehydrogenase, and cholesterol levels at higher doses, suggesting hepatotoxicity and lipid metabolism disruption. Genotoxicity analysis demonstrated increased micronucleus formation at 30 and 300 mg/kg, indicative of chromosomal instability possibly linked to oxidative stress. Histopathological evaluations revealed mild hepatocyte degeneration and hyperemia in the liver and brain tissues at the highest dose. Importantly, no significant toxic effects were observed at the 10 mg/kg dose. These findings highlight the dose-dependent toxicity of colemanite, with low doses exhibiting a favorable safety profile. This study underscores the need for dose optimization and further research to elucidate the molecular mechanisms underlying colemanite's toxicological effects, including its impact on various organs over both short-term and long-term exposures. Additionally, future studies should focus on assessing the human relevance of these effects to ensure its safe and effective therapeutic application.
硬硼钙石（COL）是一种含硼矿物，已显示出潜在的治疗应用前景，尤其是在药物递送和骨骼健康领域。然而，尽管它具有有前景的生物活性特性，但关于其安全性，尤其是其潜在医学用途，缺乏全面的毒理学数据。先前的研究主要集中在其工业应用上，对其生物学效应的研究有限。这种知识空白促使了当前的研究，该研究旨在通过行为、血液学、生化、遗传毒性和组织病理学分析来研究硬硼钙石对大鼠的亚急性毒性。在7天的时间里，给大鼠分别给予10、30和300毫克/千克的剂量。行为评估，包括运动活动和高架十字迷宫试验，表明探索行为增强，这表明好奇心或活动增强，且运动协调或类似焦虑行为没有改变。血液学结果显示血细胞比容、血红蛋白和红细胞计数呈剂量依赖性降低，而生化分析表明，在较高剂量下天冬氨酸转氨酶、乳酸脱氢酶和胆固醇水平升高，提示肝毒性和脂质代谢紊乱。遗传毒性分析表明，在30和300毫克/千克剂量下微核形成增加，表明染色体不稳定可能与氧化应激有关。组织病理学评估显示，在最高剂量下，肝脏和脑组织出现轻度肝细胞变性和充血。重要的是，在10毫克/千克剂量下未观察到明显的毒性作用。这些发现突出了硬硼钙石的剂量依赖性毒性，低剂量显示出良好的安全性。这项研究强调了剂量优化和进一步研究的必要性，以阐明硬硼钙石毒理学效应的分子机制，包括其在短期和长期暴露下对各个器官的影响。此外，未来的研究应侧重于评估这些效应与人类的相关性，以确保其安全有效的治疗应用。
