分子状水素はHMGCS2を介したβ-ヒドロキシ酪酸代謝調節によりシスプラチン誘発性腎毒性を軽減する
Using a cisplatin-induced acute kidney injury (AKI) mouse model, this study examined the renoprotective effects of H2 gas inhalation and the underlying mechanisms. H2 inhalation markedly reduced renal inflammation and apoptosis, as assessed by TUNEL staining, ELISA, and immunohistochemistry. RNA sequencing followed by KEGG pathway enrichment analysis revealed activation of the ketone body metabolic pathway, characterized by elevated expression of the ketogenic enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) and consequent enhancement of β-hydroxybutyrate (β-HOB) synthesis. A series of in vivo and in vitro validation experiments, including flow cytometry, qRT-PCR, and western blotting, confirmed that H2-driven upregulation of HMGCS2 and β-HOB was responsible for the observed renoprotective outcomes. These findings identify a metabolic mechanism by which molecular hydrogen mitigates chemotherapy-associated kidney injury.
H2 inhalation upregulates the ketogenic enzyme HMGCS2, enhancing β-hydroxybutyrate (β-HOB) synthesis. Elevated β-HOB levels subsequently suppress inflammatory signaling and apoptosis in renal tissue, thereby conferring protection against cisplatin-induced nephrotoxicity.
For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.
See also:
https://h2-papers.org/en/papers/40705191