Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Engineering Research Center of Transplantation and Immunology, Shanghai, China.
Front Immunol. 2022 May 25;13:891351. doi: 10.3389/fimmu.2022.891351. eCollection 2022.
Oxidative stress and excessive inflammatory responses are the two critical mechanisms of hepatic ischemia-reperfusion injury (HIRI) encountered in many clinical settings, including following hepatectomy and liver transplantation. Effective anti-inflammatory and anti-oxidative pharmacological interventions are urgently needed to counter HIRI. The present study showed that a biocompatible Prussian blue (PB) scavenger with reactive oxygen species (ROS) scavenging and anti-inflammatory properties might be used a promising treatment for HIRI. Following intravenous administration, PB scavenger was mainly distributed in the liver, where it showed excellent ability to alleviate apoptosis, tissue injury and organ dysfunction after HIRI. PB scavenger was found to protect liver tissue by scavenging ROS, reducing neutrophil infiltration and promoting macrophage M2 polarization. In addition, PB scavenger significantly reduced oxidative stress in primary hepatocytes, restoring cell viability under oxidative stress condition. PB scavenger effectively reduced lipopolysaccharide-stimulated inflammation in RAW 264.7 cells. These findings indicate that PB scavenger may be a potential therapeutic agent for the treatment of HIRI, providing an alternative treatment for ROS-associated and inflammatory liver diseases.
氧化应激和过度炎症反应是许多临床情况下（包括肝切除和肝移植后）肝缺血再灌注损伤（HIRI）的两个关键机制。迫切需要有效的抗炎和抗氧化药理干预来对抗 HIRI。本研究表明，具有活性氧（ROS）清除和抗炎特性的生物相容性普鲁士蓝（PB）清除剂可能是治疗 HIRI 的一种有前途的方法。静脉给药后，PB 清除剂主要分布在肝脏，在那里它表现出减轻 HIRI 后细胞凋亡、组织损伤和器官功能障碍的优异能力。PB 清除剂通过清除 ROS、减少中性粒细胞浸润和促进巨噬细胞 M2 极化来保护肝组织。此外，PB 清除剂还显著降低了原代肝细胞中的氧化应激，在氧化应激条件下恢复了细胞活力。PB 清除剂有效抑制了 RAW 264.7 细胞中脂多糖刺激的炎症反应。这些发现表明，PB 清除剂可能是治疗 HIRI 的一种有前途的治疗剂，为 ROS 相关和炎症性肝病提供了一种替代治疗方法。
