Hydrogen gas (H2) delivered by intraperitoneal injection alleviated methionine- and choline-deficient diet-induced metabolic dysfunction–associated steatotic liver disease in mice via inhibiting GSDMD- and GSDME-mediated pyroptosis

作者：Yun Chen, Kangrong Wang, Wenhai Guo, Chen Lu, Wenting Suo, Qiuling Li, Yao Deng, Xinling Chen, Min Dai, Xiao-Dong Zhang, Jingwen Xu, Wen Su, Shuangling Yang, Hongzhi Yang, Fuman Yan, Haimei Liu, Yaxin Zhang · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1575106 · 被引用次数：2 · 研究领域：Hydrogen's biological and therapeutic effects、Liver Disease Diagnosis and Treatment、Liver Disease and Transplantation

Background Hydrogen gas (H 2 ), which is the lightest and diffusible gas molecule, has strong abilities to alleviate excessive oxidative stress, inflammation, and apoptosis. Inhalation of H 2 is beneficial for preventing the damage of the lung, heart, brain, liver, kidneys, and many other organs. However, the effect of intraperitoneal injection of H 2 on metabolic dysfunction–associated steatotic liver disease (MASLD) is unclear. Objective The aim of this study is to investigate whether intraperitoneal injection of H 2 can improve MASLD, and if so, what are the key innate immune mechanisms involved? Methods The MASLD mouse model was established by feeding a methionine- and choline-deficient (MCD) diet for 3 weeks. H 2 was daily given by intraperitoneal injection since the eighth day of MCD diet feeding, and lasted for 2 weeks. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were examined to evaluate liver injury. Hematoxylin and eosin (H&E) staining, Oil Red O staining, qPCR analysis of hepatic lipid metabolism genes, and detection of hepatic triglyceride (TG) levels were performed to evaluate hepatic steatosis. Masson trichrome staining and Collagen-I and Collagen-III protein levels were used to evaluate liver fibrosis. The liver 3-nitrotyrosine (3-NT) was detected by immunoblotting and immunofluorescence, and the levels of malondialdehyde (MDA) and reduced glutathione (GSH) were measured using kits to evaluate redox homeostasis. T...