School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, China.
Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China.
J Food Biochem. 2022 Oct;46(10):e14318. doi: 10.1111/jfbc.14318. Epub 2022 Jul 13.
Alcohol abuse is a major cause of alcoholic liver disease (ALD) and can result in fibrosis and cirrhosis. γ-glutamylcysteine (γ-GC) is a precursor of glutathione (GSH) with antioxidant and anti-inflammatory properties. Our research aimed to explore the protective impact of γ-GC on ALD and its potential mechanisms of efficiency in vitro and in vivo. L02 cells were pretreated with γ-GC (20, 40, and 80 μM) for 2 h and exposed to ethanol for 24 h. Cell viability, apoptosis, oxidative stress, and inflammatory levels were measured. The expression of protein cleaved caspase-3 and cleaved PARP and flow cytometry results indicated that γ-GC decreases apoptosis on L02 cells after ethanol treatment. Moreover, γ-GC also attenuated oxidative stress and mitochondrial damage in hepatocytes caused by ethanol via increasing cellular GSH, SOD activity, and mitochondrial membrane potential. In vivo experiments, γ-GC effectively reduced the AST, ALT, and TG levels in mice. The inflammation of ALD was alleviated by γ-GC both in vivo and in vitro. Additionally, histopathological examination demonstrated that γ-GC treatment lessened lipid droplet formation and inflammatory damage. In conclusion, these results showed that γ-GC has anti-inflammatory and anti-apoptotic effects on ALD because it could help hepatocytes maintain sufficient GSH levels to combat the excess reactive oxygen species (ROS) generated during ethanol metabolism. PRACTICAL APPLICATIONS: Alcohol intake is the fifth highest risk factor for premature death and disability among all risk variables. However, few medicines are both safe and effective for the treatment of ALD. As a direct precursor of GSH, γ-GC has a broad variety of potential antioxidant and anti-inflammatory applications for the treatment of numerous medical conditions. In conclusion, these results showed that γ-GC could protect cells from ALD via suppressing oxidative stress, alleviating inflammation, and preventing apoptosis.
酒精滥用是酒精性肝病（ALD）的主要原因，并可导致纤维化和肝硬化。γ-谷氨酰半胱氨酸（γ-GC）是谷胱甘肽（GSH）的前体，具有抗氧化和抗炎特性。我们的研究旨在探索 γ-GC 对 ALD 的保护作用及其在体外和体内的潜在作用机制。L02 细胞用 γ-GC（20、40 和 80 μM）预处理 2 小时，然后用乙醇处理 24 小时。测量细胞活力、凋亡、氧化应激和炎症水平。蛋白裂解 caspase-3 和裂解 PARP 的表达和流式细胞术结果表明，γ-GC 可减少乙醇处理后 L02 细胞的凋亡。此外，γ-GC 还通过增加细胞内 GSH、SOD 活性和线粒体膜电位来减轻乙醇引起的肝细胞氧化应激和线粒体损伤。在体内实验中，γ-GC 有效降低了小鼠的 AST、ALT 和 TG 水平。γ-GC 无论是在体内还是体外都能缓解 ALD 的炎症。此外，组织病理学检查表明，γ-GC 治疗减轻了脂质滴形成和炎症损伤。总之，这些结果表明，γ-GC 对 ALD 具有抗炎和抗凋亡作用，因为它可以帮助肝细胞保持足够的 GSH 水平，以对抗乙醇代谢过程中产生的过量活性氧（ROS）。实际应用：酒精摄入是所有风险变量中导致过早死亡和残疾的第五大最高风险因素。然而，治疗 ALD 的安全有效的药物寥寥无几。作为 GSH 的直接前体，γ-GC 具有广泛的抗氧化和抗炎应用潜力，可用于治疗多种疾病。总之，这些结果表明，γ-GC 可以通过抑制氧化应激、减轻炎症和防止细胞凋亡来保护细胞免受 ALD 的侵害。
