Zhang Yaxing, Bi Mingmin, Chen Zifeng, Dai Min, Zhou Ge, Hu Yuxuan, Yang Hongzhi, Guan Weibing
Department of Traditional Chinese Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China.
Department of Otorhinolaryngology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518107, P.R. China.
Exp Ther Med. 2021 May;21(5):453. doi: 10.3892/etm.2021.9884. Epub 2021 Mar 1.
Binge alcohol drinking is fast becoming a global health concern, with the liver among the first organ involved and the one afflicted with the greatest degree of injury. Oxidative stress, alterations in hepatic metabolism, immunity and inflammation have all been reported to contribute to the development of alcoholic liver disease (ALD). Hydrogen gas (H) serves a key role in the modulation of hepatic redox, immune and inflammatory homeostasis. However, the effects of treatment using intraperitoneal injection of H on ALD remain unexplored. Therefore, the aim of the present study was to investigate the effects and underlying mechanism of intraperitoneal injection of H on acute alcohol-induced liver injury in a mouse model. H was administered by daily intraperitoneal injections (1.0 ml/100 g) for 4 days. On day 4, the mice received H after fasting for 5.5 h. After 30 min, the mice were administered with 33% (v/v) ethanol at a cumulative dose of 4.5 g/kg body weight by four equally divided gavages at 20-min intervals. Blood and liver tissues were collected at 16 h after the first ethanol gavage. Subsequently, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride and total cholesterol (TC) levels were analyzed using an Automatic Clinical Analyzer. Hepatic JNK activity and GAPDH levels were examined by western blotting. It was observed that acute ethanol gavage induced liver injury, as indicated by significantly increased serum ALT and AST levels, which were effectively decreased by H at 16 h after the first ethanol gavage. In addition, H treatment reduced serum TC levels in the Alcohol+H group when compared with those in Alcohol group. Mechanistically, H attenuated hepatic JNK phosphorylation induced by acute ethanol gavage. Therefore, the results of the present study demonstrated that treatment with exogenous H by intraperitoneal injection may alleviate acute alcohol-induced liver injury by inhibiting hepatic JNK activation, which may represent a novel therapeutic strategy for ALD.
暴饮酒精正迅速成为一个全球健康问题，肝脏是首先受累的器官之一，也是损伤程度最严重的器官。据报道，氧化应激、肝脏代谢、免疫和炎症的改变均有助于酒精性肝病（ALD）的发展。氢气（H₂）在调节肝脏氧化还原、免疫和炎症稳态中起关键作用。然而，腹腔注射H₂治疗ALD的效果仍未得到探索。因此，本研究的目的是探讨腹腔注射H₂对小鼠急性酒精性肝损伤的影响及潜在机制。通过每日腹腔注射（1.0 ml/100 g）给予H₂，持续4天。在第4天，小鼠禁食5.5小时后接受H₂。30分钟后，以20分钟的间隔通过四次等分灌胃给予小鼠33%（v/v）乙醇，累积剂量为4.5 g/kg体重。在第一次乙醇灌胃后16小时收集血液和肝脏组织。随后，使用自动临床分析仪分析血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、甘油三酯和总胆固醇（TC）水平。通过蛋白质印迹法检测肝脏JNK活性和GAPDH水平。观察到急性乙醇灌胃诱导了肝损伤，表现为血清ALT和AST水平显著升高，而在第一次乙醇灌胃后16小时，H₂有效地降低了这些水平。此外，与酒精组相比，H₂治疗降低了酒精+H₂组的血清TC水平。从机制上讲，H₂减轻了急性乙醇灌胃诱导的肝脏JNK磷酸化。因此，本研究结果表明，腹腔注射外源性H₂可能通过抑制肝脏JNK激活来减轻急性酒精性肝损伤，这可能代表了一种治疗ALD的新策略。
