Abstract
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.
Highlights
Liver disease is a significant source of global health problems
The Nonalcoholic liver injury (NLI) can gradually develop to nonalcoholic steatohepatitis, which leads to cirrhosis and hepatocellular carcinoma [2]
The structure was analyzed by Fourier transform infrared spectroscopy (FTIR; Thermo Scientific Nicolet; Waltham, MA, USA), nuclear magnetic resonance spectroscopy (NMR; Bruker AVANCE NEO; Karlsruhe, Baden-Württemberg, Germany), and high-resolution mass spectra (HRMS; Finnigan LTQ-FT instrument; Waltham, MA, USA), respectively
Summary
Liver disease is a significant source of global health problems. Nonalcoholic liver injury (NLI), including nonalcoholic fatty liver (NAFL), and drug- and poison-induced liver injury, is becoming a challenge to human health worldwide [1]. Despite the growing public health impact of NLI, therapeutic strategy is limited and there is still a lack of clinically approved therapies. Excess free radical accumulation is an important cause of NLI [3]. In NAFL patients, abnormal lipid metabolism induces the imbalance of redox homeostasis and the increase in free radical levels in hepatocytes [4]. The free radicals can cause lipid peroxidation, and destroy the structure and function of protein and DNA, leading to membrane rupture and cell death. Improving hepatocyte anti-free radical capacity has been considered an effective strategy in treating the liver injury
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