Hydrogen Gas Protects Kidneys from Cancer Drug Side Effects in Mice
- Authors
- Yan Tian, Huilan Su, Yunxi Chen, Xiaomeng Geng, Yafang Zhang, Yu Wang, Wenjie Tang, Weiping Fan, Jianjun Zhou, Youzhen Wei
- Journal
- Molecular Biology Reports
- Year
- 2025
- DOI
- 10.1007/s11033-025-10845-0
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Cisplatin-Induced Nephrotoxicity
- Body System
- Renal
TL;DR
Inhaling hydrogen gas protected the kidneys from chemotherapy damage by reducing inflammation and boosting beneficial ketone metabolism.
Key Finding
Molecular hydrogen gas protected mouse kidneys from cisplatin-induced damage by activating a metabolic pathway that produces β-hydroxybutyrate, which reduced inflammation and cell death in kidney tissue.
Summary
This study tested whether molecular hydrogen (H2 gas) could protect mouse kidneys from damage caused by cisplatin, a chemotherapy drug. Researchers found that H2 inhalation reduced kidney injury by decreasing inflammation and cell death. The protective effect appeared to work by activating a metabolic pathway that produces β-hydroxybutyrate, a compound that helps protect kidney tissue.
Practical Takeaway
This early-stage mouse study suggests H2 may help protect kidneys during chemotherapy, but it's important to note this research has not been tested in humans yet. The findings are preliminary and much more research would be needed before any clinical application. Anyone undergoing chemotherapy should discuss kidney protection strategies only with their oncology team.
Abstract
Background: Nephrotoxicity is a common adverse effect of many chemotherapeutic agents and represents a major dose-limiting factor in cancer treatment. Therefore, developing effective renoprotective strategies is urgently needed. Molecular hydrogen (H2) has emerged as a therapeutic agent with potent antioxidant and anti-inflammatory properties, selectively scavenging hydroxyl radicals and alleviating tissue injury. However, the protective effects and underlying mechanisms of H2 in chemotherapy-induced acute kidney injury (AKI) remain poorly understood. Methods: A cisplatin-induced AKI mouse model was established with or without H₂ administration. Kidney injury biomarkers were evaluated, and levels of inflammation and apoptosis were assessed using TUNEL staining, ELISA, and immunohistochemistry. To investigate the underlying mechanisms, RNA sequencing was performed, followed by heatmap, Venn diagram, and volcano plot analyses to identify differentially expressed genes. KEGG pathway enrichment analysis was used to explore metabolic alterations upon H2 treatment in cisplatin-induced nephrotoxicity. Subsequently, metabolic alterations were validated through a series of in vivo and in vitro experiments, including ELISA, flow cytometry, qRT-PCR, western blotting, and immunohistochemistry. Results: H2 inhalation significantly attenuated cisplatin-induced kidney injury by reducing inflammation and apoptosis in renal tissue. Transcriptomic analysis revealed that H2 upregulated the ketone body metabolic pathway, particularly enhancing β-hydroxybutyrate (β-HOB) synthesis via increased expression of the ketogenic enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2). Functional assays confirmed that H2-mediated upregulation of HMGCS2 and β-HOB contributed to its renoprotective effects. Conclusion: Molecular hydrogen confers protection against cisplatin-induced nephrotoxicity by modulating β-HOB metabolism through upregulation of HMGCS2, thereby suppressing renal inflammation and apoptosis. These findings provide new insights into the metabolic mechanism underlying H2's tissue-protective effects and offer a theoretical foundation for its potential clinical application in mitigating chemotherapy-induced kidney injury.