Abstract：
BACKGROUND: Haematitum, a time-honored mineral-based Chinese medicine, has been used medicinally in China for over 2000 years. It is now included in the Chinese Pharmacopoeia and used clinically for treating digestive and respiratory diseases. The Chinese Materia Medica records that it is toxic and should not be taken for a long period, but there are few research reports on the toxicity of Haematitum and its potential toxicity mechanisms.
OBJECTIVE: This study aimed to evaluate the toxicity of Haematitum and calcined Haematitum, including organ toxicity, neurotoxicity, and reproductive toxicity. Further, it is also necessary to explore the mechanism of Haematitum toxicity and to provide a reference for the safe clinical use of the drug.
METHODS: The samples of Haematitum and calcined Haematitum decoctions were prepared. KM mice were treated with samples by gavage for 10 days, and lung damage and apoptosis were assessed by HE staining and TUNEL staining of lung tissues respectively. Metabolomics analysis was performed by HPLC-MS. Metallomics analysis was performed by ICP-MS. In addition, C. elegans was used as a model for 48 h exposure to examine the neurotoxicity and reproductive toxicity-related indices of Haematitum, including locomotor behaviors, growth and development, reproductive behaviors, AChE activities, sensory behaviors, apoptosis, and ROS levels.
RESULTS: The use of large doses of Haematitum decoction caused lung damage in mice. Neither calcined Haematitum decoction nor Haematitum decoction at clinically used doses showed organ damage. Metabolomics results showed that disorders in lipid metabolic pathways such as sphingolipid metabolism and glycerophospholipid metabolism may be important factors in Haematitum-induced pulmonary toxicity. High doses of Haematitum decoction caused neurological damage to C. elegans, while low doses of Haematitum decoction and calcined Haematitum decoction showed no significant neurotoxicity. Decoction of Haematitum and calcined Haematitum did not show reproductive toxicity to C. elegans. Toxicity was also not observed in the control group of iron (Ⅱ) and iron (Ⅲ) ions in equal amounts with high doses of Haematitum.
CONCLUSIONS: Haematitum is relatively safe for routine doses and short-term use. Calcination can significantly reduce Haematitum toxicity, and this study provides a reference for safe clinical use.
OBJECTIVE: This study aimed to evaluate the toxicity of Haematitum and calcined Haematitum, including organ toxicity, neurotoxicity, and reproductive toxicity. Further, it is also necessary to explore the mechanism of Haematitum toxicity and to provide a reference for the safe clinical use of the drug.
METHODS: The samples of Haematitum and calcined Haematitum decoctions were prepared. KM mice were treated with samples by gavage for 10 days, and lung damage and apoptosis were assessed by HE staining and TUNEL staining of lung tissues respectively. Metabolomics analysis was performed by HPLC-MS. Metallomics analysis was performed by ICP-MS. In addition, C. elegans was used as a model for 48 h exposure to examine the neurotoxicity and reproductive toxicity-related indices of Haematitum, including locomotor behaviors, growth and development, reproductive behaviors, AChE activities, sensory behaviors, apoptosis, and ROS levels.
RESULTS: The use of large doses of Haematitum decoction caused lung damage in mice. Neither calcined Haematitum decoction nor Haematitum decoction at clinically used doses showed organ damage. Metabolomics results showed that disorders in lipid metabolic pathways such as sphingolipid metabolism and glycerophospholipid metabolism may be important factors in Haematitum-induced pulmonary toxicity. High doses of Haematitum decoction caused neurological damage to C. elegans, while low doses of Haematitum decoction and calcined Haematitum decoction showed no significant neurotoxicity. Decoction of Haematitum and calcined Haematitum did not show reproductive toxicity to C. elegans. Toxicity was also not observed in the control group of iron (Ⅱ) and iron (Ⅲ) ions in equal amounts with high doses of Haematitum.
CONCLUSIONS: Haematitum is relatively safe for routine doses and short-term use. Calcination can significantly reduce Haematitum toxicity, and this study provides a reference for safe clinical use.
摘要：
背景：血液，一种历史悠久的矿物中药，在中国已经使用了2000多年的药物。现已列入中国药典，临床用于治疗消化和呼吸系统疾病。中药记载它有毒性,不宜长期服用,但关于Hematum的毒性及其潜在毒性机制的研究报道较少。
目的：本研究旨在评估血热和煅烧血热的毒性，包括器官毒性，神经毒性，和生殖毒性。Further,探讨该药物的毒性作用机制,为临床安全用药提供参考。
方法:制备血汤和煅烧血汤样品。通过管饲法用样品处理KM小鼠10天，肺组织HE染色和TUNEL染色分别评估肺损伤和细胞凋亡。通过HPLC-MS进行代谢组学分析。通过ICP-MS进行金属组学分析。此外,C.elegans被用作48小时暴露的模型，以检查血液的神经毒性和生殖毒性相关指标，包括运动行为，成长和发展，生殖行为,AChE活动,感官行为，凋亡，和ROS水平。
结果：使用大剂量的血药汤会引起小鼠的肺损伤。临床使用剂量的煅烧血痰汤和血痰汤均未显示器官损伤。代谢组学结果表明，鞘脂代谢和甘油磷脂代谢等脂质代谢途径的紊乱可能是引起血痰肺毒性的重要因素。高剂量的血药汤对秀丽隐杆线虫造成神经损害，低剂量血痰汤和煅烧血痰汤无明显神经毒性。血汤和煅烧血汤对秀丽隐杆线虫没有生殖毒性。铁(Ⅱ)和铁(Ⅲ)离子等量高剂量的对照组也未观察到毒性。
结论：对于常规剂量和短期使用，Hematitum是相对安全的。煅烧可以显着降低血液毒性，为临床安全使用提供参考。
目的：本研究旨在评估血热和煅烧血热的毒性，包括器官毒性，神经毒性，和生殖毒性。Further,探讨该药物的毒性作用机制,为临床安全用药提供参考。
方法:制备血汤和煅烧血汤样品。通过管饲法用样品处理KM小鼠10天，肺组织HE染色和TUNEL染色分别评估肺损伤和细胞凋亡。通过HPLC-MS进行代谢组学分析。通过ICP-MS进行金属组学分析。此外,C.elegans被用作48小时暴露的模型，以检查血液的神经毒性和生殖毒性相关指标，包括运动行为，成长和发展，生殖行为,AChE活动,感官行为，凋亡，和ROS水平。
结果：使用大剂量的血药汤会引起小鼠的肺损伤。临床使用剂量的煅烧血痰汤和血痰汤均未显示器官损伤。代谢组学结果表明，鞘脂代谢和甘油磷脂代谢等脂质代谢途径的紊乱可能是引起血痰肺毒性的重要因素。高剂量的血药汤对秀丽隐杆线虫造成神经损害，低剂量血痰汤和煅烧血痰汤无明显神经毒性。血汤和煅烧血汤对秀丽隐杆线虫没有生殖毒性。铁(Ⅱ)和铁(Ⅲ)离子等量高剂量的对照组也未观察到毒性。
结论：对于常规剂量和短期使用，Hematitum是相对安全的。煅烧可以显着降低血液毒性，为临床安全使用提供参考。
