Cantharidin (CTD), a compound secreted from Mylabris species, exhibits strong antitumor properties; however, hepatotoxicity restricts its clinical application. The mechanism by which CTD induces toxicity remains unclear. In the present study, the hepatotoxicity of CTD in the rat was investigated using a metabolomic approach combined with conventional pathology methods. A total of 30 rats were intragastrically treated with two doses of CTD (0.75 and 1.5 mg/kg) for 15 days to evaluate hepatotoxicity. Serum and liver samples were collected for biochemical dynamics analyses, histopathological examination and metabolomic analysis. It was found that liver index and serum biochemical indices were significantly increased. Furthermore, the pathology results showed that hepatocytes and subcellular organelles were damaged. Metabolomics analysis found 4 biomarkers in serum and 15 in the liver that were associated with CTD‐induced hepatotoxicity. In addition, these were responsible for CTD hepatotoxicity by glycerophospholipid metabolism, sphingolipid metabolism, and steroid hormone biosynthesis. In conclusion, conventional pathology and metabolomics for exploring hepatotoxicity can provide useful information about the safety and potential risks of CTD.

中文翻译：

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血清和肝脏代谢组学结合常规病理学方法研究斑蝥素致大鼠肝毒性的机制。

斑蝥素 (CTD)，一种从Mylabris分泌的化合物物种，具有很强的抗肿瘤特性；然而，肝毒性限制了其临床应用。CTD 诱导毒性的机制尚不清楚。在本研究中，使用代谢组学方法结合常规病理学方法研究了 CTD 在大鼠中的肝毒性。总共 30 只大鼠用两种剂量的 CTD（0.75 和 1.5 毫克/千克）灌胃治疗 15 天，以评估肝毒性。收集血清和肝脏样本用于生化动力学分析、组织病理学检查和代谢组学分析。发现肝脏指标和血清生化指标显着升高。此外，病理结果显示肝细胞和亚细胞器受损。代谢组学分析发现血清中有 4 种生物标志物，肝脏中有 15 种生物标志物与 CTD 诱导的肝毒性有关。此外，这些是由甘油磷脂代谢、鞘脂代谢和类固醇激素生物合成引起的 CTD 肝毒性的原因。总之，用于探索肝毒性的常规病理学和代谢组学可以提供有关 CTD 安全性和潜在风险的有用信息。