Protective effect of platinum nano-antioxidant and nitric oxide against hepatic ischemia-reperfusion injury

• Published in: Nature communications Vol. 13; no. 1; pp. 2513 - 12
• Main Authors: Mu, Jing, Li, Chunxiao, Shi, Yu, Liu, Guoyong, Zou, Jianhua, Zhang, Dong-Yang, Jiang, Chao, Wang, Xiuli, He, Liangcan, Huang, Peng, Yin, Yuxin, Chen, Xiaoyuan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.05.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 59; 631/1647/767/1424; 631/61/54; 639/166/985; 639/925/352; 692/308/2778; Animals; Antioxidants; Antioxidants - pharmacology; Antioxidants - therapeutic use; Cascade chemical reactions; Catalysis; Cell activation; Chemical synthesis; Cytokines; Humanities and Social Sciences; Humans; Inflammation; Injury prevention; Ischemia; Leukocytes (neutrophilic); Liver; Liver - metabolism; Liver diseases; Macrophages; Metal-organic frameworks; Mice; multidisciplinary; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Oxidative stress; Oxygen; Platinum; Platinum - pharmacology; Platinum - therapeutic use; Reactive oxygen species; Reactive Oxygen Species - pharmacology; Reperfusion; Reperfusion Injury - drug therapy; Reperfusion Injury - prevention & control; Scavenging; Science; Science (multidisciplinary); Therapeutic applications; Transplantation; Zeolites
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-29772-w

Therapeutic interventions of hepatic ischemia-reperfusion injury to attenuate liver dysfunction or multiple organ failure following liver surgery and transplantation remain limited. Here we present an innovative strategy by integrating a platinum nanoantioxidant and inducible nitric oxide synthase into the zeolitic imidazolate framework-8 based hybrid nanoreactor for effective prevention of ischemia-reperfusion injury. We show that platinum nanoantioxidant can scavenge excessive reactive oxygen species at the injury site and meanwhile generate oxygen for subsequent synthesis of nitric oxide under the catalysis of nitric oxide synthase. We find that such cascade reaction successfully achieves dual protection for the liver through reactive oxygen species clearance and nitric oxide regulation, enabling reduction of oxidative stress, inhibition of macrophage activation and neutrophil recruitment, and ensuring suppression of proinflammatory cytokines. The current work establishes a proof of concept of multifunctional nanotherapeutics against ischemia-reperfusion injury, which may provide a promising intervention solution in clinical use. Pharmacological interventions against hepatic ischemia-reperfusion injury remain limited. Here, the authors provide a nanotherapeutics-based solution combining reactive oxygen species scavenging and nitric oxide modulation.