Preadministration of Hydrogen-Rich Water Protects Against Lipopolysaccharide-Induced Sepsis and Attenuates Liver Injury

Abstract

Despite significant advances in antibiotic therapy and intensive care, sepsis remains the most common cause of death in intensive care units. We previously reported that molecular hydrogen (H2) acts as a therapeutic and preventive antioxidant. Here, we show that preadministration of H2-dissolved water (HW) suppresses lipopolysaccharide (LPS)-induced endotoxin shock in mice. Drinking HW for 3 days before LPS injection prolonged survival in a mouse model of sepsis. The H2 concentration immediately increased in the liver but not in the kidney after drinking HW. The protective effects of the preadministration of HW on LPS-induced liver injury were examined. Twenty-four hours after LPS injection, preadministration of HW reduced the increase in both apoptosis and oxidative stress. Moreover, preadministration of HW enhanced LPS-induced expression of heme oxyganase-1 and reduced endothelin-1 expression. These results indicate the therapeutic potential of HW in preventing acute injury of the liver with attenuation of an increase in oxidative stress. HW is likely to trigger adaptive responses against oxidative stress.

Anti-oxidant and anti-inflammatory effects of hydrogen-rich water alleviate ethanol-induced fatty liver in mice

“…Unfortunately, the limited sensitivity of the ELISA kit prevented us from analyzing endotoxins in the present study. However, previous studies reported that H 2 alleviated endotoxin-induced liver injury in rodents by reducing inflammation and cell apoptosis[20,22,23]. Taken together, the evidence indicates that HRW administration helps maintain permeability, mucosal structure and barrier function in intestine and improves the gastrointestinal microenvironment for bacteria that protect against EtOH-induced liver injury.…”

“…Similar antioxidant phenomena were observed in many oxidative stress-related diseases, especially CCl 4 - , endotoxin-, acetaminophen- and ischemia / reperfusion -induced hepatic injuries in rodents[21-27,32,40]. A number of studies reported that H 2 reduces oxidative stress not only directly but also indirectly, by regulating anti-oxidative signal transduction, including nuclear factor erythroid 2-related factor 2 (Nrf-2) and sirtuin 1 (Sirt1)[14,18,20,35]. Antioxidants regulated by Nrf-2 via an antioxidant response element-driven mechanism include SOD, GSH-Px, CAT, heme oxygenase-1 (HO-1), peroxiredoxins, etc [48].…”

Administration of hydrogen-rich water prevents vascular aging of the aorta in LDL receptor-deficient mice

“…Activation of these CDK inhibitors generates ROS, which act as signaling molecules to promote the continuous induction of cellular senescence 30 . Remarkably, drinking HW ameliorates oxidative stress in animal disease models, including the Apoe −/− mouse model of atherosclerosis 16 , and in human clinical trials, including metabolic syndrome 17 , 31 and rheumatoid arthritis 32 . One possible mechanistic explanation for the suppressive effect of HW on cellular senescence is that the lowering of ROS by HW downregulates DDR pathways.…”

“…For example, drinking HW ameliorated symptoms of Parkinson’s disease in a rat model, whereas both H 2 gas inhalation and lactulose-induced production of intestinal H 2 did not 15 . We recently reported that pre-administration of HW was sufficient to attenuate septic inflammation in mice, strongly indicating that the therapeutic effects of HW derive from a mechanism distinct from the direct reduction of ROS by H 2 16 .…”

Therapeutics for Inflammatory-Related Diseases Based on Plasmon-Activated Water: A Review

“…Notably, H 2 has no risk of flammability or explosion at a concentration of less than 4.7% in air, as commented by the authors. Since then, hydrogen-rich water has been widely used as alternatively therapeutic topics on many medical diseases [ 14 , 15 , 16 , 17 , 18 ]. Moreover, acidic cosmetic water acts against Staphylococcus aureus , has anti-inflammatory properties, and is a superoxide anion radical scavenger [ 19 ].…”