LC−MS/MS-based arachidonic acid metabolomics in acute spinal cord injury reveals the upregulation of 5-LOX and COX-2 products

• Published in: Free radical biology & medicine 2022-11, Vol.193 (Pt 1), p.363-372
• Main Authors: Pang, Yilin, Liu, Xinjie, Zhao, Chenxi, Shi, Xuelian, Zhang, Jiawei, Zhou, Tiangang, Xiong, Haoning, Gao, Xiang, Zhao, Xiaoqing, Yang, Xingjian, Ning, Guangzhi, Zhang, Xu, Feng, Shiqing, Yao, Xue
• Format: Article
• Language: English
• Subjects: 5-Lipoxygenase; Animals; Arachidonic acid; Arachidonic Acid - metabolism; Chromatography, Liquid; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Dinoprostone - metabolism; Leukotriene B4; Metabolomics; Rats; Spinal Cord Injuries; Spinal cord injury; Tandem Mass Spectrometry; Up-Regulation
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2022.10.303

Arachidonic acid (AA) plays a critical role in inflammatory regulation and secondary injury after spinal cord injury (SCI). However, the overall AA metabolism profile in the acute phase of SCI remains elusive. Here we quantified AA metabolomics by High Performance Liquid Chromatography−Tandem Mass Spectrometry-Based Method (LC−MS/MS) using spinal cord tissue collected at 4 h, 24 h and 48 h after contusive SCI in rats. Remarkably, Prostaglandin E2 (PGE2) and Leukotriene B4 (LTB4) were significantly increased throughout the acute SCI. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), the key enzymes involved in the production of PGE2 and LTB4, were elevated in the lesioned spinal cord tissue, validated by both western blot and immunofluorecnce. The spatial-temporal changes of COX-2 and 5-LOX mainly occurs in neurons both in epicenter and rostral and caudal spinal cord segments after SCI. Our study sheds light on the dynamic microenvironment changes in acute SCI by characterizing the profile of AA metabolism. The COX-2 and 5-LOX may be promising therapeutic target for SCI. [Display omitted] •Quantitative arachidonic acid metabolomics profiles based on LC-MS/MS were characterized in the acute spinal cord injury.•Prostaglandin E2 (PGE2) and Leukotriene B4 (LTB4) increased significantly after spinal cord injury.•Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) are the key mediators in the acute spinal cord injury.