Therapeutic Effects of Hydrogen Gas Inhalation on Trimethyltin-Induced Neurotoxicity and Cognitive Impairment in the C57BL/6 Mice Model.

Abstract

A trimethyltin (TMT)-induced neurotoxicity model was established in C57BL/6 mice via a single intraperitoneal injection of 2.6 mg/kg TMT. Animals subsequently received 2% H2 gas inhalation for 30 minutes daily over four weeks. Spatial recognition memory assessed by Y-maze was impaired in TMT-only animals but recovered in the H2-treated group. In both serum and brain tissue, levels of ROS, nitric oxide, MDA, Apo-E, Aβ-40, phospho-tau, and Bax were reduced following H2 inhalation, while pro-inflammatory cytokines G-CSF, IL-6, and TNF-α declined significantly. Conversely, Bcl-2 and VEGF expression increased after H2 exposure. Catalase and GPx activities, which were elevated in the TMT-only group, normalized with H2 inhalation. Collectively, these findings indicate that 2% H2 gas inhalation suppresses oxidative stress, neuroinflammation, and Alzheimer's disease-related biomarkers while improving cognitive performance in a TMT mouse model, suggesting a potential role for H2 in addressing neurodegenerative conditions involving cognitive decline.

Mechanism

H2 inhalation is proposed to reduce oxidative stress markers (ROS, MDA, NO), suppress pro-inflammatory cytokines (TNF-α, IL-6, G-CSF), downregulate pro-apoptotic Bax, and upregulate anti-apoptotic Bcl-2 and VEGF, collectively providing neuroprotection in TMT-challenged mice.