Hydrogen Gas Therapy in Schizophrenia: Potential Neuroprotective Effects From an Animal Study.

Abstract

AIMS: Oxidative stress has recently emerged as a key factor in the pathophysiology of schizophrenia. This study investigated whether inhalation therapy with hydrogen gas, a selective antioxidant, could reduce oxidative stress and improve behavioral outcomes in an MK-801-induced schizophrenia-like mouse model. METHODS: Six-week-old male C57BL/6 mice received chronic intraperitoneal injections of MK-801 (0.5 mg/kg) or saline for 4 weeks. A third group received MK-801 followed by hydrogen gas inhalation therapy. Behavioral assessments included the open-field test (OFT) to evaluate hyperactivity as an indicator of positive symptoms and the prepulse inhibition (PPI) test to assess cognitive dysfunction. Oxidative stress was evaluated by measuring whole-brain hydroxyl radical antioxidant capacity (HORAC) and total antioxidant capacity (TAC). RESULTS: MK-801-treated mice exhibited significant hyperactivity in the OFT and a trend toward impaired PPI, confirming the schizophrenia-like phenotype. Hydrogen gas treatment did not produce significant improvements. MK-801 administration significantly reduced HORAC levels, whereas hydrogen gas therapy markedly restored them. No significant differences in TAC were observed among the groups. CONCLUSION: These findings suggest that hydrogen gas therapy does not significantly ameliorate behavioral abnormalities in the MK-801-induced schizophrenia-like mouse model but exerts beneficial antioxidant effects. Future studies should evaluate hydrogen gas as an adjunctive therapy and further assess its efficacy and safety in clinical settings.