Pharmacokinetics of hydrogen administered intraperitoneally as hydrogen-rich saline and its effect on ischemic neuronal cell death in the brain in gerbils

Hirano, Momoko; Sugai, Kazuhisa; Fujisawa, Masahiko; Kobayashi, Eiji; Katsumata, Yoshinori; Hakamata, Yoji; Sano, Motoaki

doi:10.1371/journal.pone.0279410

Cited by 4 publications

(5 citation statements)

References 31 publications

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“…It is possible that the effect of HRW on recovery sleep is specific to the active phase because sleep pressure is already near its ceiling immediately following 6 hours of sleep deprivation. While direct observation of HRW half-life post-HRW-administration in mice (by gas chromatography, for example) has not been previously reported, data from other model species suggests that H 2 persists in the body for a few hours, though its protective effects post-administration in small mammals may last several days [ 43 ]. While we report changes in behavioral markers of sleep pressure (time to sleep onset, NREM amount, and sleep consolidation), a mixed-effects analysis with multiple comparisons and Benjamini and Hochberg correction reveals no effect of HRW on NREM relative delta power during undisturbed conditions nor during the recovery from sleep loss ( Figure 5 ).…”

Section: Discussionmentioning

confidence: 99%

Hydrogen-rich water improves sleep consolidation and enhances forebrain neuronal activation in mice

Vincent,

Madani,

Dikeman

et al. 2023

Sleep Advances

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Study Objectives Sleep loss contributes to various health issues and impairs neurological function. Molecular hydrogen has recently gained popularity as a non-toxic ergogenic and health promoter. The effect of molecular hydrogen on sleep and sleep-related neural systems remains unexplored. This study investigates the impact of hydrogen-rich water (HRW) on sleep behavior and neuronal activation in sleep-deprived mice. Methods Adult C57BL/6J mice were implanted with electroencephalography (EEG) and electromyography (EMG) recording electrodes and given HRW (0.7 -1.4 mM) or regular water for 7 days ad libitum. Sleep-wake cycles were recorded under baseline conditions and after acute sleep loss. Neuronal activation in sleep- and wake-related regions was assessed using cFos immunostaining. Results HRW increased sleep consolidation in undisturbed mice and increased non-rapid eye movement (NREM) and rapid-eye movement (REM) sleep amount in sleep-deprived mice. HRW also decreased the average amount of time for mice to fall asleep after light onset. Neuronal activation in the lateral septum, medial septum, ventrolateral preoptic area, and median preoptic area was significantly altered in all mice treated with HRW. Conclusions HRW improves sleep consolidation and increases neuronal activation in sleep-related brain regions. It may serve as a simple, effective treatment to improve recovery after sleep loss.

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Section: Discussionmentioning

confidence: 99%

Hydrogen-rich water improves sleep consolidation and enhances forebrain neuronal activation in mice

Vincent,

Madani,

Dikeman

et al. 2023

Sleep Advances

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“…In conclusion, although there have been many animal and clinical studies examining the efficacy of H 2 on various diseases, few pharmacokinetic animal studies regarding H 2 have been conducted to extrapolate the results to humans. Therefore, our research group has clarified the pharmacokinetics of H 2 in the body via experiments using single and continuous inhalation of H 2 [33,35], drinking of H 2 -rich water (transcatheter injection of H 2 -rich water into the jejunum) [32], and intraperitoneal injection of H 2 -rich saline solutions [10].…”

Section: Discussionmentioning

confidence: 99%

“…The H 2 concentrations of the blood were measured using previously described methods [10,32]. Briefly, 1 ml of blood was collected in a 10-ml sealed vial and 100 μl of water was collected in a 100-ml sealed vial.…”

Section: Measurements Of Blood and Bathwater H 2 Concentrationsmentioning

confidence: 99%

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Direct evidence of hydrogen absorption from the skin – a pig study

Iwai¹,

Kobayashi²,

Kobayashi³

et al. 2023

Arch Med Sci Civil Dis

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IntroductionIt has not been experimentally proven whether hydrogen gas (H2) is absorbed into the body through the skin by hydrogen-rich hot-water bathing.Material and methodsIn this study, Hairless mini pigs, whose skin closely resembles that of humans, were bathed in hydrogen (H2)-rich hot water to assess the absorption of H2 through the skin. An H2-rich water generation line was developed to maintain a high concentration of H2 via the circulation of hot water in an 80-litre bathtub. Two hairless mini pigs (14.2 ±1.4 kg, 60 days old, 1 male and 1 female) were first placed in the H2-dissolved bath. After a washout period, one pig was bathed in an H2-dissolved bath and the other in a bath containing no H2 for 20 min. During the experiment, blood was collected from the pigs’ jugular vein, carotid artery, inferior vena cava (IVCs), and portal vein to measure the blood H2 concentration.ResultsThe H2 concentration at the IVC of the pig in the H2-dissolved bath increased from 0.733 ±0.636 ppb (w/w) to 16.9 ±4.46 ppb (w/w) after 2 min, 37.2 ±13.8 ppb (w/w) after 10 min, and 45.7 ±7.73 ppb (w/w) (H2 saturation level: 3%) after 20 min. The blood H2 concentration levels of the pig in the non-H2 bath remained below the detection limit of 0.3 ppb.ConclusionsBathing in water with a high concentration of dissolved hydrogen was considered an effective means of supplying H2 to skin tissues and beyond.

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“…In this study, we focused on preventive therapy before the occurrence of events such as ischemia. Specifically, we used ischemia/reperfusion gerbil models [8], which are a subset of rats prone to hyperlipidemia. Under normal dietary conditions, gerbils exhibit triglyceride (TG) levels exceeding 300 mg/dL.…”

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confidence: 99%

Pre-Administration of Blackberry Extracts in Induced Ischemia Reperfusion Events in Rodents

Oda,

Hakamata,

Kobayashi

2023

Metabolites

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Blackberries are abundant in substances that have antioxidative and other effects, and technologies for enhancing the effectiveness of their incorporation into the body are being developed. The effectiveness of such substances has been investigated in various models, including rodent ischemia models. While a test substance can be administered either before or after an event, healthy foods are generally pre-administered prophylactically in experiments. Pre-administration may have the potential to elevate the blood concentration of the active substance sufficiently prior to the event and/or induce adaptive changes in the ischemic tolerance of the recipient through long-term pre-administration. Based on the recently reported 2-week pre-administration of blackberries in a rat model, we investigated the pre-administration of blackberry extracts in a hyperlipidemia model using Mongolian gerbils. We then discussed the effects of the pre-administration on the treated animals before an ischemic event.

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Pharmacokinetics of hydrogen administered intraperitoneally as hydrogen-rich saline and its effect on ischemic neuronal cell death in the brain in gerbils

Cited by 4 publications

References 31 publications

Hydrogen-rich water improves sleep consolidation and enhances forebrain neuronal activation in mice

Hydrogen-rich water improves sleep consolidation and enhances forebrain neuronal activation in mice

Direct evidence of hydrogen absorption from the skin – a pig study

Pre-Administration of Blackberry Extracts in Induced Ischemia Reperfusion Events in Rodents

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