College of Food Science and Technology, Northwest University, Xi'an 710069, Shaanxi, China; Laboratory of Nutritional and Healthy Food-Individuation Manufacturing Engineering, Xi'an 710069, Shaanxi, China; Research Center of Food Safety Risk Assessment and Control, Xi'an 710069, Shaanxi, China.
College of Food Science and Technology, Northwest University, Xi'an 710069, Shaanxi, China; Laboratory of Nutritional and Healthy Food-Individuation Manufacturing Engineering, Xi'an 710069, Shaanxi, China; Research Center of Food Safety Risk Assessment and Control, Xi'an 710069, Shaanxi, China.
Food Res Int. 2023 Apr;166:112546. doi: 10.1016/j.foodres.2023.112546. Epub 2023 Feb 1.
Patulin (PAT), a toxin produced by molds in fruits and related products, has caused frequent food poisoning incidents worldwide. However, its potential mechanism of hepatotoxicity remains presently unclear. Herein, we intragastrically administered the C57BL/6J mice with 0, 1, 4, and 16 mg/kg b.wt of PAT on a single occasion (acute model), and 0, 50, 200, and 800 μg/kg b.wt of PAT daily over two weeks (subacute model). Assessments of histopathology and aminotransferase activities confirmed that significant hepatic damages were induced. Metabolic profiling on the liver using ultra-high-performance liquid chromatography high-resolution mass spectrometry discovered 43 and 61 differential metabolites in two models, respectively. Notably, acute and subacute models shared the common 18 differential metabolites, among which N-acetyl-leucine, inosine, 2-O-methyladenosine, PC 40:7, PC 38:6, and PC 34:2 could be regarded as the biomarkers indicative of PAT exposure. Moreover, analysis of metabolic pathways demonstrated that pentose phosphate pathway and purine metabolism were the main altered pathways in the acute model. Nevertheless, more pathways related to amino acids were affected in the subacute model. These results reveal the comprehensive influence of PAT on hepatic metabolism and provide a deeper understanding of the hepatotoxicity mechanism of PAT.
棒曲霉素（PAT）是一种由水果及相关产品中的霉菌产生的毒素，已在全球范围内引发了频繁的食物中毒事件。然而，其潜在的肝毒性机制目前尚不清楚。在此，我们单次给 C57BL/6J 小鼠灌胃 0、1、4 和 16 mg/kg bw 的 PAT（急性模型），以及每天灌胃 0、50、200 和 800 μg/kg bw 的 PAT 共两周（亚急性模型）。组织病理学和转氨酶活性评估证实了明显的肝损伤。使用超高效液相色谱-高分辨质谱对肝脏进行代谢组学分析，分别在两个模型中发现了 43 种和 61 种差异代谢物。值得注意的是，急性和亚急性模型共有 18 种共同的差异代谢物，其中 N-乙酰亮氨酸、肌苷、2-O-甲基腺苷、PC 40:7、PC 38:6 和 PC 34:2 可被视为指示 PAT 暴露的生物标志物。此外，代谢途径分析表明，戊糖磷酸途径和嘌呤代谢是急性模型中主要受影响的途径。然而，亚急性模型中更多与氨基酸相关的途径受到了影响。这些结果揭示了 PAT 对肝脏代谢的全面影响，并深入了解了 PAT 的肝毒性机制。
