We have reported that hydrogen (H 2 ) acts as an efficient antioxidant by gaseous rapid diffusion. When water saturated with hydrogen (hydrogen water) was placed into the stomach of a rat, hydrogen was detected at several mM level in blood. Because hydrogen gas is unsuitable for continuous consumption, we investigated using mice whether drinking hydrogen water ad libitum, instead of inhaling hydrogen gas, prevents cognitive impairment by reducing oxidative stress. Chronic physical restraint stress to mice enhanced levels of oxidative stress markers, malondialdehyde and 4-hydroxy-2-nonenal, in the brain, and impaired learning and memory, as judged by three different methods: passive avoidance learning, object recognition task, and the Morris water maze. Consumption of hydrogen water ad libitum throughout the whole period suppressed the increase in the oxidative stress markers and prevented cognitive impairment, as judged by all three methods, whereas hydrogen water did not improve cognitive ability when no stress was provided. Neural proliferation in the dentate gyrus of the hippocampus was suppressed by restraint stress, as observed by 5-bromo-2 0 -deoxyuridine incorporation and Ki-67 immunostaining, proliferation markers. The consumption of hydrogen water ameliorated the reduced proliferation although the mechanistic link between the hydrogen-dependent changes in neurogenesis and cognitive impairments remains unclear. Thus, continuous consumption of hydrogen water reduces oxidative stress in the brain, and prevents the stress-induced decline in learning and memory caused by chronic physical restraint. Hydrogen water may be applicable for preventive use in cognitive or other neuronal disorders.

Hydrogen has potential for improving the quality of life of patients during chemotherapy by efficiently mitigating the side effects of cisplatin.

Rationale: Caloric restriction (CR) confers cardioprotection against ischemia/reperfusion injury. However, the exact mechanism(s) underlying CR-induced cardioprotection remain(s) unknown. Recent evidence indicates that Sirtuins, NAD ؉ -dependent deacetylases, regulate various favorable aspects of the CR response. Thus, we hypothesized that deacetylation of specific mitochondrial proteins during CR preserves mitochondrial function and attenuates production of reactive oxygen species during ischemia/reperfusion. Objective:The objectives of the present study were (1) to investigate the effect of CR on mitochondrial function and mitochondrial proteome and (2) to investigate what molecular mechanisms mediate CR-induced cardioprotection. Methods and Results:Male 26-week-old Fischer344 rats were randomly divided into ad libitum-fed and CR (40% reduction) groups for 6 months. No change was observed in basal mitochondrial function, but CR preserved postischemic mitochondrial respiration and attenuated postischemic mitochondrial H 2 O 2 production. CR decreased the level of acetylated mitochondrial proteins that were associated with enhanced Sirtuin activity in the mitochondrial fraction. We confirmed a significant decrease in the acetylated forms of NDUFS1 and cytochrome bc1 complex Rieske subunit in the CR heart. Low-dose Resveratrol treatment mimicked the effect of CR on deacetylating them and attenuated reactive oxygen species production during anoxia/reoxygenation in cultured cardiomyocytes without changing the expression levels of manganese superoxide dismutase. Treatment with nicotinamide completely abrogated the effect of low-dose Resveratrol. Key Words: ischemia Ⅲ mitochondria Ⅲ nutrition Ⅲ reactive oxygen species Ⅲ reperfusion T he prevalence of cardiovascular diseases increases with age. 1 Mortality of coronary artery disease in the elderly is higher than that in the middle-aged. 2,3 Consistent with clinical investigations, experimental studies demonstrate that hearts from senescent animals are more susceptible to ischemia than those from young animals. 4 -6 Both age-related increased prevalence of systemic diseases, referred to as cardiovascular risk factors, and development of cardiovascular aging contribute to the association between aging and cardiovascular diseases. 1 Therefore, development of novel therapeutics for the purpose of controlling cardiovascular aging is urgently required to provide for population aging in developed countries. Conclusions:Caloric restriction (CR) has been widely investigated in experimental animals as a powerful intervention that can prevent and reverse age-related changes. [7][8][9] The daily caloric intake in CR-treated animals was 50% to 70% of the average food intake of animals fed ad libitum (AL). Although there is no evidence stating that CR prolongs lifespan in humans, it markedly increases life span in several species, including rhesus monkey. 7,10 In addition, there is mounting evidence Original received February 17, 2011; revision received June 14, 2011; accepted J...