Oral intake of hydrogen-rich water inhibits intimal hyperplasia in arterialized vein grafts in rats

Abstract

─ 79 ─ 【Objective】Gastric cancer patients have high proportions of malnutrition, which may become much deteriorated after gastrectomy. As we know, malnourished subjects have high risk of morbidities and mortality. Oral Nutritional Supplements (ONS) is a potential supplement, which may restore the nutritional status of gastric cases. In this study, we study the role of ONS in gastric cancer cases after gastrectomy. 【Methods】We designed one prospective randomized international study, enrolling the gastric cancer cases in National Taiwan University Hospital (NTUH) and The University of Tokyo Hospital. Tokyo University studyONS group was orally-administrated 400kcal per day liquid diet in addition to usual diet for 12 weeks postoperatively. The primary end-point was change of body weight. The second end-points included change of nutritional characteristic, body composition (fat and muscle), and QOL (EORTC QLOQ-C30)． 【Result】There were 113 patients in this study, including 40 total gastrectomy (TG) and 73 distal gastrectomy (DG). For TG, body weight loss at ONS group (n=23) was significantly less than at c o n t r o l g r o u p (n = 1 7). A m o n g t h e b o d y components for TG, muscle loss at ONS group showed borderlinely significant less at ONS group compared with control group. However, there were no significance differences in body weight loss between ONS (n=41) and control group (n=32) receiving DG. 【Conclusion】The nutritional status of TG group was significantly worse than DG group. ONS therapy is useful for TG group to decrease the loss of body weight. Postoperative use of ONS therapy in TG cases may be advised to improve postoperative nutritional status. Arterialized vein grafts often fail due to intimal hyperplasia (IH), which remains a serious concern for patients after arterial bypass surgery, due to a lack of pharmacological agents that prevent IH. Hydrogen gas potently protects organs and cells from many insults via its antiinflammatory, antiapoptotic, and antioxidant properties. We investigated the efficacy of the oral administration of hydrogen-rich water (HW), a feasible approach for hydrogen intake, for prevention of IH. The inferior vena cava was excised from donor rats, stored in cold Ringer solution for 2 hours, and placed as an interposition graft in the abdominal aorta of syngeneic Lewis rats. HW for drinking was generated by immersing a magnesium stick in tap water (Mg + 2H2O → Mg (OH) 2 + H2). Beginning on the day of graft implantation, recipients were given either regular tap water (RW), HW, or HW that had subsequently been degassed. mRNA levels were quantitated by real-time RT-PCR. Smooth muscle cell migration in culture was assessed using A7r5 cells. Six weeks after grafting, the grafts in the rats given RW or degassed HW had developed IH. However, IH was significantly suppressed in rats given HW. One week after grafting, upregulation of the mRNAs for ICAM and endothelin receptor? A in the vein grafts was attenuated in the rats receiving HW. In culture, hydrogen treatment for 24 hours red...

Hydrogen Therapy in Cardiovascular and Metabolic Diseases: from Bench to Bedside

“…Similarly, intraperitoneal injection of H 2 -rich saline has been reported to ameliorate aortic hypertrophy and improve endothelium-dependent vascular relaxation and baroreflex function in spontaneously hypertensive rats (SHR) [30]. Drinking H 2 -rich water reduced endothelial denudation, macrophage infiltration, and neointimal formation in vein grafts by reducing the activation of p38 MAPK inflammatory cascades, and decreasing the expression and activity of MMP-2 and MMP-9 [31]. H 2 -rich saline also prevents neointimal hyperplasia induced by carotid balloon injury in rat by suppressing ROS and the TNF-α/NF-κB signaling pathway [32], and inactivating the Ras-MEK1/2 - extracellular signal-regulated kinase1/2 (ERK1/2) and Akt signaling pathways [33].…”

“…H 2 -rich medium inhibits Ang II-induced proliferation and migration of VSMCs in vitro by blocking ROS-dependent ERK1/2, p38 MAPK, c-Jun NH 2 -terminal kinase (JNK) and ezrin/radixin/moesin signaling [29]. However, the Atsunori Nakao group [31] indicated that H 2 -rich medium inhibits VSMCs migration with or without FBS, but has no effects on proliferation.…”

Hydrogen does not exert neuroprotective effects or improve functional outcomes in rats after intracerebral hemorrhage

“…Recently, strong clinical and experimental evidence has shown that hydrogen, administered by gas inhalation or ingestion of an aqueous hydrogen-containing solution, has potent protective cellular effects in various diseases (4,5,10,20,21,24,26,27), but without major adverse effects (5). Previous studies have shown that hydrogen has antioxidant, anti-apoptotic, antiinflammatory, and cytoprotective properties that are beneficial to the cell (5).…”

“…Hydroxyl radicals and peroxynitrites are very strong ROS that react indiscriminately with nucleic acids, lipids, and proteins, resulting in DNA fragmentation, lipid peroxidation, and protein inactivation (4,5,10,20,21,24,26,27). edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent scavenger of hydroxyl radicals and is used for the treatment of ischemic stroke in Japan.…”

Hydrogen-supplemented drinking water protects cardiac allografts from inflammation-associated deterioration

“…Drinking water containing molecular hydrogen potently protected kidney allografts from chronic rejection by inhibition of inflammatory responses through mitogen‐activated protein kinases [11]. Likewise, drinking hydrogen‐rich water prevented intimal hyperplasia in arterialized vein grafts and was associated with inhibition of inflammatory cytokines and activation of matrix metalloproteinases [12].…”