Because of its widespread use, the pharmaceutical acetaminophen (APAP) is frequently detected in aquatic environments. APAP can have serious physiological effects, such as reduced reproduction, low growth rates, and abnormal behavior, in aquatic organisms. However, the methods available for evaluation of the aquatic toxicity of APAP are of limited usefulness. The present study aimed to develop reliable and sensitive markers for evaluation of APAP toxicity using Daphnia as a model organism. We focused on N-acetyl-p-benzoquinoneimine (NAPQI) production from APAP via cytochrome P450 metabolism because NAPQI causes APAP toxicity. Daphnia magna were exposed to APAP (0, 50, or 100 mg/L for 12 h or 24 h), and the total metabolites were extracted and analyzed for NAPQI. Direct detection of NAPQI was difficult because of its high reactivity, and its peak was close to that for APAP. Therefore, we tried to identify molecular and biochemical indicators associated with NAPQI generation, elimination, and its interactions with macromolecules. We identified changes in CYP370A13 gene expression, glutathione depletion, inhibition of thioredoxin reductase activity, and production of reactive oxygen species as indicators of D. magna exposure to APAP. These indicators could be used to develop sensitive and accurate techniques to evaluate the environmental toxicity of APAP.

由于其广泛使用，在水生环境中经常检测到对乙酰氨基酚（APAP）药物。APAP在水生生物中会产生严重的生理影响，例如繁殖减少，生长速度低和行为异常。但是，可用于评估APAP的水生毒性的方法用途有限。本研究旨在开发可靠和敏感的标记物，以水蚤作为模型生物来评估APAP毒性。由于NAPQI会引起APAP毒性，因此我们重点研究了APAP通过细胞色素P450代谢产生的N-乙酰基-对-苯并醌亚胺（NAPQI）。水蚤将其暴露于APAP（0、50或100 mg / L，持续12 h或24 h），然后提取总代谢物并分析NAPQI。由于NAPQI的高反应性，因此难以直接检测，并且其峰值接近于APAP的峰值。因此，我们试图确定与NAPQI产生，消除及其与大分子相互作用有关的分子和生化指标。我们确定CYP370A13基因表达，谷胱甘肽耗竭，硫氧还蛋白还原酶活性的抑制和活性氧的产生的变化，作为D. magna暴露于APAP的指标。这些指标可用于开发敏感和准确的技术，以评估APAP的环境毒性。