GNF-5837 attenuates acute liver injury by inhibiting oxidative stress

Background: Acute liver injury is caused by various reasons and results in abnormal liver function, serving as the basis for various liver diseases. However, there has not been much progress in research on the prevention and treatment of acute liver injury, and drugs directly or specifically used for acute liver injury are still lacking. Recent studies have shown that several types of cell death are closely associated with the onset, progression, and prognosis of liver injury.

Methods and results: In this study, we identified a small molecule compound, GNF-5837, which attenuates the severity of acute liver injury by inhibiting Apoptosis, Pyroptosis, and Ferroptosis. Mechanically, we found that GNF-5837 reduces the generation of Reactive Oxygen Species (ROS) and alleviates oxidative stress by capturing excessive oxidative free radicals generated during cell death, which effectively inhibits Apoptosis, Pyroptosis, and Ferroptosis. The results of animal experiments showed that GNF-5837 can effectively alleviate Con A-induced acute liver injury in vivo by blocking multiple modes of cell death.

Conclusions: Therefore, our research indicates that the small molecule compound GNF-5837 is an oxygen radical scavenger with significant peroxide removal effects, which offer a potential therapeutic approach for cell death caused by imbalances in intracellular oxidative stress levels and provides new insights into the study of acute liver injury.

Acute liver injury; Cell death; Oxidative stress.