Abstract
BACKGROUND: Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia, leading to severe systemic complications and reduced quality of life. Current therapies often fail to comprehensively alleviate diabetic complications, highlighting the need for novel approaches. Animal studies and clinical trials have demonstrated the therapeutic potential of molecular hydrogen (H(2)), particularly in controlling DM. However, no systematic studies have investigated the long-term treatment effects of hydrogen-rich water (HRW) on DM, and the underlying mechanisms remain largely unknown. This study aims to explore the therapeutic efficacy of HRW in mitigating DM-related complications and uncover its molecular mechanisms using a streptozotocin (STZ)-induced diabetic rat model. METHODS: The therapeutic effects and mechanisms of HRW were evaluated through RNA sequencing (RNA-seq) analysis of multiple organs from STZ-induced diabetic male rat models after 24 weeks of HRW administration. Parameters such as fasting blood glucose (FBG), body weight (BW), and general condition were monitored. At week 24, tissues from the eyes, testes, penis, sperm, liver, kidneys, stomach, colon, and bones were collected and subjected to hematoxylin and eosin staining. RNA-seq was conducted on fresh testis, liver, kidney, and stomach tissues to identify differentially expressed genes. RESULTS: Long-term administration of HRW significantly decreased FBG levels and increased BW, indicating an improvement in metabolic control. HRW also ameliorated various DM-related complications, including diabetic cataracts, bone loss, diabetic nephropathy, erectile dysfunction, asthenozoospermia, and renal neoplasms. RNA-seq and bioinformatic analyses revealed significant enrichment of metabolic pathway-related genes in testis, liver, kidney, and stomach tissues, suggesting the reprogramming of metabolic functions. The findings suggest that oral ingestion of HRW is a safe, effective, and convenient treatment that improves quality of life for DM patients by reducing blood glucose levels and alleviating diabetic complications. CONCLUSIONS: This study advances the understanding of HRW's therapeutic mechanisms, particularly its ability to reprogram metabolic pathways. HRW shows promise as an alternative treatment for diabetes, offering a proactive approach to improving metabolic health and alleviating related complications.