Department of Intensive and Intermediate Care, University Hospital Aachen, Aachen, Germany.
Department of Anesthesiology, University Hospital Aachen, Aachen, Germany.
Sci Rep. 2021 Mar 18;11(1):6302. doi: 10.1038/s41598-021-85859-2.
N-acetyl-para-amino phenol (APAP, usually named paracetamol), which is commonly used for its analgesic and antipyretic properties may lead to hepatotoxicity and acute liver damage in case of overdoses. Released cytokines and oxidative stress following acute liver damage may affect other organs' function notably the diaphragm, which is particularly sensitive to oxidative stress and circulating cytokines. We addressed this issue in a mouse model of acute liver injury induced by administration of APAP. C57BL/6J mice (each n = 8) were treated with N-acetyl-para-amino phenol (APAP) to induce acute drug caused liver injury and sacrificed 12 or 24 h afterwards. An untreated group served as controls. Key markers of inflammation, proteolysis, autophagy and oxidative stress were measured in diaphragm samples. In APAP treated animals, liver damage was proven by the enhanced serum levels of alanine aminotransferase and aspartate aminotransferase. In the diaphragm, besides a significant increase in IL 6 and lipid peroxidation, no changes were observed in key markers of the proteolytic, and autophagy signaling pathways, other inflammatory markers and fiber dimensions. The first 24 h of acute liver damage did not impair diaphragm atrophic pathways although it slightly enhanced IL-6 and lipid peroxidation. Whether longer exposure might affect the diaphragm needs to be addressed in future experiments.
N-乙酰对氨基酚（APAP，通常称为扑热息痛）因其具有镇痛和解热作用而被广泛应用，但如果过量使用可能会导致肝毒性和急性肝损伤。急性肝损伤后释放的细胞因子和氧化应激可能会显著影响其他器官的功能，特别是膈肌，膈肌对氧化应激和循环细胞因子特别敏感。我们在 APAP 诱导的急性肝损伤小鼠模型中研究了这个问题。C57BL/6J 小鼠（每组 n=8）接受 N-乙酰对氨基酚（APAP）治疗，以诱导急性药物引起的肝损伤，并在 12 或 24 小时后处死。未处理的组作为对照。在膈肌样本中测量炎症、蛋白水解、自噬和氧化应激的关键标志物。在 APAP 处理的动物中，通过增强的血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平证明了肝损伤。在膈肌中，除了 IL6 和脂质过氧化的显著增加外，蛋白水解和自噬信号通路的关键标志物、其他炎症标志物和纤维尺寸没有变化。尽管急性肝损伤的前 24 小时稍微增加了 IL-6 和脂质过氧化，但并未损害膈肌萎缩途径。更长时间的暴露是否会影响膈肌需要在未来的实验中解决。
