Pharmacokinetics of hydrogen after ingesting a hydrogen-rich solution: A study in pigs

Ichihara, Genki; Katsumata, Yoshinori; Moriyama, Hidenori; Kitakata, Hiroki; Hirai, Akeo; Momoi, Mizuki; Ko, Seien; Shinya, Yoshiki; Kinouchi, Kenichiro; Kobayashi, Eiji; Sano, Motoaki

doi:10.1016/j.heliyon.2021.e08359

Cited by 17 publications

(19 citation statements)

References 25 publications

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“…The results showed that the concentration of H 2 in tissues depended on the time, the concentration of exogenous H 2 intake as well as the characteristics of the tissue itself. After the exogenous H 2 was inhaled by mice, it diffused through the alveoli into the bloodstream, then dissolved, and was transported through the whole body in a blood flow-dependent manner ( Ichihara et al., 2021 ) despite of the unclear receptor molecules and downstream effectors ( Sano et al., 2020 ). Instead of being concentrated in the blood vessels, H 2 diffused out of the blood vessels during travelling ( Sano et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Accurate in vivo real-time determination of the hydrogen concentration in different tissues of mice after hydrogen inhalation

Zhu

Liu

et al. 2022

Heliyon

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Section: Discussionmentioning

confidence: 99%

Accurate in vivo real-time determination of the hydrogen concentration in different tissues of mice after hydrogen inhalation

Zhu

Liu

et al. 2022

Heliyon

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“…To prepare H 2 -rich saline, a polyethylene terephthalate bottle was filled with saline; then, H 2 was pressurized with a DAYS hydrogen gas filling system (Doctors Man Co., Ltd., Japan) and filled into the bottle to a gauge pressure of 0.4 MPa, as described previously [ 4 ]. The bottle was shaken for 30 seconds to dissolve the H 2 , and then the lid was opened to reduce the pressure to atmospheric pressure.…”

Section: Methodsmentioning

confidence: 99%

“…Although the efficacy of molecular H 2 has been reported extensively, its pharmacokinetics and pharmacodynamics after administration were first investigated only recently: We performed a study in which we measured the blood concentration of H 2 in miniature pigs after inhalation of H 2 [ 5 , 11 ] and injection of H 2 water into the intestinal tract [ 4 ]; the study showed that after a single inhalation of H 2 gas, the H 2 concentration in carotid arterial blood rises quickly but drops below the detection limit within a few minutes [ 12 ]. H 2 in the blood appears to be rapidly excreted through exhalation.…”

Section: Introductionmentioning

confidence: 99%

“…H 2 in the blood appears to be rapidly excreted through exhalation. By administering 500 ml of H 2 -rich water through a tube inserted into the jejunum of miniature pigs, we confirmed that H 2 was absorbed into the blood through the jejunal wall and flowed into the portal vein and hepatic superior inferior vena cava (IVC); however, almost all of it was expired and only a little reached the carotid artery [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2022

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Intraperitoneal administration of hydrogen (H2)-containing saline inhibited neuronal cell death in ischemic stroke in a number of animal models, but it is unknown whether H2 is absorbed from the abdominal cavity into the blood and reaches the brain. In this study, we investigated whether intraperitoneal administration of saline containing H2 inhibits neuronal cell death caused by cerebral ischemia and measured the concentration of H2 in the carotid artery and inferior vena cava (IVC). Gerbils were subjected to transient unilateral cerebral ischemia twice, and saline or H2-rich saline was administered intraperitoneally three or seven times every 12 hours. We evaluated the number of apoptotic cells in the hippocampus and cerebral cortex on day 3 and the number of viable neurons in the hippocampus and cerebral cortex on day 7. In addition, a single dose of saline or H2-rich saline was administered intraperitoneally, and blood H2 levels in the carotid artery and IVC were measured. On day 3 of ischemia/reperfusion, the number of neurons undergoing apoptosis in the cortex was significantly lower in the H2-rich saline group than in the saline group, and on day 7, the number of viable neurons in the hippocampus and cerebral cortex was significantly higher in the H2-rich saline group. Intraperitoneal administration of H2-rich saline resulted in large increases in H2 concentration in the IVC ranging from 0.00183 mg/L (0.114%) to 0.00725 mg/L (0.453%). In contrast, carotid H2 concentrations remained in the range of 0.00008 mg/L (0.0049%) to 0.00023 (0.0146%). On average, H2 concentrations in carotid artery were 0.04 times lower than in IVC. These results indicate that intraperitoneal administration of H2-rich saline significantly suppresses neuronal cell death after cerebral ischemia, even though H2 hardly reaches the brain.

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“…The animal experiments were conducted following the Guide for the Care and Use of Laboratory Animals (Icjihara et al, 2021) and approved by Institutional Animal Care and Use Committee, Jeju National University (Jeju, Korea) for Animal ethics. Twenty-four Sprague Dawley rats of each gender were obtained from the SAMTAKO Inc. (Osan, Korea) at 6 weeks of age and used after two weeks adaptation period.…”

Section: Animalsmentioning

confidence: 99%

Cytotoxicity and acute toxicity evaluation of hydrogen-rich Gynostemma pentaphyllum Makino distillate

Kim

2022

JANS

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Hydrogen-rich Gynostemma pentaphyllum Makino distillate (HRGD) consists of Gynostemma pentaphyllum Makino steam distillate with hydrogen gas. Although both G. pentaphyllum Makino and hydrogen-rich water are well known for their biological and medical benefits, there is a lack of information on their safety and toxicity in vivo acute oral toxicity test and in vitro cytotoxicity method. The current study aimed to assess the cytotoxicity and acute oral toxicity of HRGD as a part of a safety evaluation using rat and human cell models. HRGD was administered orally once by gavage to male and female Sprague-Dawley rats at doses of 0, 2500, and 5000 mg/kg. Cytotoxicity assay was conducted in vitro at various concentrations in 10 different human normal and cancer cell lines; TK6 (human normal lymphomablastoid cells), Chang (human hepatic cells), 16HBE14o- (human bronchial epithelial cells), URotsa (human urothelium cells), MCF (human breast cancer cells), Hela (human cervical cancer cells), A375 (human malignant melanoma cells), HCT116 (human colon cancer cells), HepG2 (human liver cancer cells) and A549 (human non-small cell lung adenocarcinoma cells). From a 14-day study in rats, we observed no compound-related changes in mortality, clinical signs, body weight, food/water consumption, organ weight and gross pathology in all dose group. The result of in vivo acute toxicity shows that no observed adverse effect level of HRGD was below 5000 mg/kg for both sexes of rats, and the minimal lethal dose was considered to be more than 5000 mg/kg. HRGD also had no in vitro cytotoxicity against all tested cells. The present study data indicated that HRGD may contain bioactive compounds of potential therapeutic significance that are relatively safe from toxic effects.

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Pharmacokinetics of hydrogen after ingesting a hydrogen-rich solution: A study in pigs

Cited by 17 publications

References 25 publications

Accurate in vivo real-time determination of the hydrogen concentration in different tissues of mice after hydrogen inhalation

Accurate in vivo real-time determination of the hydrogen concentration in different tissues of mice after hydrogen inhalation

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

Cytotoxicity and acute toxicity evaluation of hydrogen-rich Gynostemma pentaphyllum Makino distillate

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