Dimeric Histidine as a Novel Free Radical Scavenger Alleviates Non-Alcoholic Liver Injury

Non-alcoholic liver injury (NLI) is a common disease worldwide. Since free radical damage in the liver is a crucial initiator leading to diseases, scavenging excess free radicals has become an essential therapeutic strategy. To enhance the antioxidant capacity of histidine, we synthesized a protonated dimeric histidine, H-bihistidine, and investigated its anti-free radical potential in several free-radical-induced NLI. Results showed that H-bihistidine could strongly scavenge free radicals caused by H₂O₂, fatty acid, and CCl₄, respectively, and recover cell viability in cultured hepatocytes. In the animal model of nonalcoholic fatty liver injury caused by high-fat diet, H-bihistidine reduced the contents of transaminases and lipids in serum, eliminated the liver's fat accumulation, and decreased the oxidative damage. Moreover, H-bihistidine could rescue CCl₄-induced liver injury and recover energy supply through scavenging free radicals. Moreover, liver fibrosis prepared by high-fat diet and CCl₄ administration was significantly alleviated after H-bihistidine treatment. This study suggests a novel nonenzymatic free radical scavenger against NLI and, potentially, other free-radical-induced diseases.