Mechanism of minocycline activating Nrf2/Hmox1 pathway to prevent ferroptosis and alleviate acute compartment syndrome

• Published in: Journal of orthopaedic surgery and research 2024-10, Vol.19 (1), p.686-20, Article 686
• Main Authors: Liao, Xiong, Huang, Zhao, Ling, He, Li, Wencai, Liu, Junjie, Lao, Yonghui, Su, Wei
• Format: Article
• Language: English
• Subjects: Acute compartment syndrome; Acute Disease; Animals; Compartment Syndromes - drug therapy; Disease Models, Animal; Ferroptosis; Ferroptosis - drug effects; Genes; Heme Oxygenase (Decyclizing); Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Male; Medical research; Medicine, Experimental; Minocycline; Minocycline - pharmacology; Minocycline - therapeutic use; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscles; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Nrf2/Hmox1 signaling pathway; Prognosis; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects
• ISSN: 1749-799X; 1749-799X
• DOI: 10.1186/s13018-024-05183-z

Acute compartment syndrome(ACS) is a perilous consequence of trauma. Acute compartment syndrome's precise cause is yet unknown. We performed studies to confirm that acute compartment syndrome can be relieved by suppressing ferroptosis and activating the Nrf2/Hmox1 pathway. We generated an ACS rat model and we conducted next-generation sequencing(NGS) of skeletal muscle tissue and identified differentially expressed target genes. Ultimately, we performed in vivo experiments to validate the presence of ferroptosis and the Nrf2/Hmox1 pathway in ACS rats. After the minocycline intervention, the drug was evaluated for its effects on ACS by examining changes associated with ferroptosis. The bioinformatics analysis identified that the genetic changes in the disease were mostly focused on ferroptosis, with noticeable modifications in Nrf2/Hmox1. Based on the in vivo results, it was observed that ACS rats exhibited significantly elevated levels of ferroptosis compared to the control rats. The suppression of the Nrf2/Hmox1 pathway mediated by minocycline improves outcomes in ACS and reduces tissue damage after intervention. Minocycline hinders ferroptosis via stimulating the Nrf2/Hmox1 pathway, which slows down the advancement of acute compartment syndrome.