Molecular hydrogen improves type 2 diabetes through inhibiting oxidative stress

Abstract

The aim of the present study was to investigate the potential therapeutic effects of molecular hydrogen on type 2 diabetes mellitus (T2DM) in rats. Following maintenance on a high-fat diet for 4 weeks, a T2DM model was established using an injection of 30 mg/kg streptozotocin via the caudal vein into Sprague-Dawley rats. On day 0 and Day 80, the blood samples were obtained from each rat for the measurement of biochemical indicators including blood lipids, fasting blood glucose, hepatic glycogen, fasting serum insulin, insulin sensitivity index, insulin resistance index, serum superoxide dismutase (SOD) and serum malondialdehyde (MDA) using an automatic biochemical analyzer. The kidneys and pancreas tissues were harvested for HE staining and Western blot assay of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), phosphorylated (p)-p65, p65, p-IκB and IκB. The results showed that in rats with T2DM, molecular hydrogen treatment decreased fasting blood glucose levels, increased hepatic glycogen synthesis and improved insulin sensitivity. Treatment with molecular hydrogen also increased the production of SOD whilst decreasing the production of MDA. In addition, molecular hydrogen alleviated the pathological changes exhibited by pancreatic islets and kidney during T2DM. Mechanistically, molecular hydrogen decreased TLR4 and MyD88 expression levels whilst also decreasing p65 and NF-κB inhibitor phosphorylation. In conclusion, molecular hydrogen exerted therapeutic effects against T2DM by improving hyperglycemia and inhibiting oxidative stress through mechanisms that are associated with the TLR4/MyD88/NF-κB signaling pathway.

Hydrogen-Rich Water Ameliorates Pancreatic Cell Necrosis and Regulates Cytokine Levels in Streptozotocin-Induced Diabetic Rats

“…36 Hyperglycemic conditions lead to high ROS production and decreased endogenous antioxidants. 37 In both in vitro and in vivo experiments, HW at 0.5-0.6 ppm showed antioxidant activity. 31 H2 molecules are biologically active gases that can be used to improve various systemic pathological conditions.…”

“…In this study, it was found that HW supplementation restored glucose levels in DM rats to nearnormal levels. Ming et al (2020) 37 reported a decreased malondialdehyde (MDA) levels in the serum of T2DM mice model after treatment with HW. H2 molecules increase the synthesis of hepatic glycogen, improve glucose intake in the liver, and lowers fasting blood glucose levels.…”

Molecular and Cellular Mechanisms Associated with Effects of Molecular Hydrogen in Cardiovascular and Central Nervous Systems

“…Molecular hydrogen reduces oxidative stress not only directly, but also indirectly by inducing antioxidation systems, including heme oxygenase-1 (HO-1) [ 60 , 61 ], superoxide dismutase (SOD) [ 7 , 9 ], catalase [ 62 ], and myeloperoxidase ( Figure 1 ) [ 62 , 63 ]. In a rat model of traumatic brain injury, it was observed that the beneficial effects of hydrogen inhalation were mediated by the reduction of oxidative stress and the stimulation of enzymatic activities of the endogenous antioxidants SOD and catalase [ 64 ].…”

“…An important factor in modulating responses to oxidative stress, and a major mechanism underlying the cellular protective effects of hydrogen, is the upregulation of the expression of genes that encode several antioxidant enzymes ( Figure 1 ) [ 7 , 9 , 62 ]. Kawamura et al [ 66 ] reported that inhalation of hydrogen gas during exposure to hyperoxia improved blood oxygenation, reduced inflammation, and induced HO-1 expression in the lung.…”

“…Molecular hydrogen is currently recognized as an emerging therapeutic, as its supplemental application exerts protective effects in cardiovascular diseases [ 1 , 2 ], neurodegenerative diseases [ 3 ], inflammatory diseases [ 4 ], neuromuscular disorders [ 5 ], metabolic syndrome [ 6 ] diabetes [ 7 , 8 ], kidney disorders [ 9 , 10 ], and cancer [ 11 ]. The protective effects of molecular hydrogen are largely related to its antiapoptotic, anti-inflammatory, and antioxidative actions ( Figure 1 ).…”