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Topiroxostat ameliorates oxidative stress and inflammation in sepsis-induced lung injury
Haiying Fu1, Junjie Zhang1, Mayu Huang2
1Emergency Department, Tong Ren Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Sepsis-induced lung injury was the most common cause of death in patients. Topiroxostat, a novel xanthine oxidoreductase inhibitors, possessed obvious organ protectives effects. Xanthine oxidase played a vital role in acute lung injury. The study aimed to investigate the roles of Topiroxostat in sepsis-induced lung injury. The sepsis rats were established using cecum ligation and perforation. The lung damage induced by sepsis was evaluated by Hematoxylin and Eosin staining and lung tissue wet to dry ratio. The oxidative stress was detected by measurement of reactive oxygen species, malondialdehyde, myeloperoxidase and superoxide dismutase (SOD). The pro-inflammatory mediators, tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and monocyte chemotactic protein 1, were measured by Enzyme-Linked Immunosorbent Assay. The cell apoptosis in lung was detected by TUNNEL staining and western blot analysis of apoptosis-related proteins including pro-apoptosis proteins, Bax, cleaved caspase9, cleaved caspase3 and anti-apoptosis protein Bcl2. The results showed that Topiroxostat significantly reduced lung damage, along with decreased oxidative stress, inflammation response and apoptosis in sepsis rats. Topiroxostat exerted markedly protective effects in sepsis-induced lung injury and could be an antioxidant in treating sepsis-induced lung injury.
Insights
Topiroxostat, a xanthine oxidoreductase inhibitor, protects against sepsis-induced lung injury by reducing oxidative stress, inflammation, and apoptosis. This antioxidant may be a promising treatment for this critical condition.
Area of Science:
- Pharmacology
- Toxicology
- Pathology
Background:
- Sepsis-induced lung injury is a leading cause of mortality.
- Xanthine oxidase plays a critical role in the pathogenesis of acute lung injury.
- Topiroxostat is a novel xanthine oxidoreductase inhibitor with known organ-protective effects.
Purpose of the Study:
- To investigate the therapeutic potential of Topiroxostat in a rat model of sepsis-induced lung injury.
- To evaluate the effects of Topiroxostat on oxidative stress, inflammation, and apoptosis in sepsis-induced lung injury.
Main Methods:
- Sepsis was induced in rats via cecum ligation and perforation.
- Lung injury was assessed using Hematoxylin and Eosin staining and wet-to-dry ratio.
- Oxidative stress markers (ROS, MDA, MPO, SOD), inflammatory mediators (TNF-α, IL-1β, IL-6, MCP-1), and apoptosis (TUNNEL, Western blot) were measured.
Main Results:
- Topiroxostat treatment significantly attenuated lung damage in septic rats.
- The drug markedly decreased levels of oxidative stress markers.
- Topiroxostat reduced pro-inflammatory cytokine levels and inhibited apoptosis in lung tissue.
Conclusions:
- Topiroxostat demonstrates significant protective effects against sepsis-induced lung injury.
- The compound acts as an antioxidant, mitigating oxidative stress, inflammation, and apoptosis.
- Topiroxostat shows potential as a novel therapeutic agent for sepsis-induced lung injury.
