EXPERIMENTAL RESEARCH
Direct evidence of hydrogen absorption from the skin – a pig study
,
 
,
 
,
 
 
 
 
More details
Hide details
1
Laboratory of Small Animal Surgery 2, School of Veterinary Medicine, Kitasato University Towada City, Aomori, Japan
 
2
Endowed Chair for the Promotion of Minipig Research, School of Veterinary Medicine, Kitasato University, Towada City, Aomori, Japan
 
3
Kobayashi Regenerative Research Institute, LLC. Wakayama-shi, Wakayama-ken, Japan
 
4
Center for Molecular Hydrogen Medicine, Keio University, Minato-ku, Tokyo, Japan
 
5
Department of Basic Sciences, School of Veterinary Nursing and Technology, Faculty of Veterinary Sciences, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo, Japan
 
6
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
 
 
Submission date: 2023-04-03
 
 
Acceptance date: 2023-05-08
 
 
Publication date: 2023-06-30
 
 
Arch Med Sci Civil Dis 2023;8(1):9-17
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
It 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 methods:
In 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.

Results:
The 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.

Conclusions:
Bathing in water with a high concentration of dissolved hydrogen was considered an effective means of supplying H2 to skin tissues and beyond.

 
REFERENCES (35)
1.
Iuchi K, Imoto A, Kamimura N, et al. Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators. Sci Rep 2016; 6: 18971.
 
2.
Shirakawa K, Kobayashi E, Ichihara G, et al. H2 inhibits the formation of neutrophil extracellular traps. JACC Basic Transl Sci 2022; 7: 146-61.
 
3.
Hayashida K, Sano M, Kamimura N, et al. Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management. Circulation 2014; 130: 2173-80.
 
4.
Hayashida K, Sano M, Ohsawa I, et al. Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun 2008; 373: 30-5.
 
5.
Matsuoka T, Suzuki M, Sano M, et al. Hydrogen gas inhalation inhibits progression to the “irreversible” stage of shock after severe hemorrhage in rats. J Trauma Acute Care Surg 2017; 83: 469-75.
 
6.
Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 2007; 13: 688-94.
 
7.
Sugai K, Tamura T, Sano M, et al. Daily inhalation of hydrogen gas has a blood pressure-lowering effect in a rat model of hypertension. Sci Rep 2020; 10: 20173.
 
8.
Ohsawa I, Nishimaki K, Yamagata K, Ishikawa M, Ohta S. Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochem Biophys Res Commun 2008; 377: 1195-8.
 
9.
Zhang Y, Su WJ, Chen Y, et al. Effects of hydrogen-rich water on depressive-like behavior in mice. Sci Rep 2016; 6: 23742.
 
10.
Hirano M, Sugai K, Fujisawa M, et al. Pharmacokinetics of hydrogen administered intraperitoneally as hydrogen-rich saline and its effect on ischemic neuronal cell death in the brain in gerbils. PLoS One 2022; 17: e0279410.
 
11.
Zhu Q, Wu Y, Li Y, et al. Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques. Sci Rep 2018; 8: 8051.
 
12.
Kobayashi E, Sano M. Organ preservation solution containing dissolved hydrogen gas from a hydrogen-absorbing alloy canister improves function of transplanted ischemic kidneys in miniature pigs. PLoS One 2019; 14: e0222863.
 
13.
Nishi K, Iwai S, Tajima K, Okano S, Sano M, Kobayashi E. Prevention of chronic rejection of marginal kidney graft by using a hydrogen gas-containing preservation solution and adequate immunosuppression in a miniature pig model. Front Immunol 2021; 11: 626295.
 
14.
Oharazawa H, Igarashi T, Yokota T, et al. Protection of the retina by rapid diffusion of hydrogen: administration of hydrogen-loaded eye drops in retinal ischemia-reperfusion injury. Invest Ophthalmol Vis Sci 2010; 51: 487-92.
 
15.
Braverman IM. Ultrastructure and organization of the cutaneous microvasculature in normal and pathologic states. J Invest Dermatol 1989; 93 (2 Suppl): 2S-9S.
 
16.
Grice EA, Segre JA. The skin microbiome [published correction appears in Nat Rev Microbiol. 2011 Aug;9(8):626]. Nat Rev Microbiol 2011; 9: 244-53.
 
17.
Higgins JC, Eady RA. Human dermal microvasculature: I. Its segmental differentiation. Light and electron microscopic study. Br J Dermatol 1981; 104: 117-29.
 
18.
Lavker RM, Kwong F, Kligman AM. Changes in skin surface patterns with age. J Gerontol 1980; 35: 348-54.
 
19.
Nakamizo S, Egawa G, Honda T, Nakajima S, Belkaid Y, Kabashima K. Commensal bacteria and cutaneous immunity. Semin Immunopathol 2015; 37: 73-80.
 
20.
Holbrook KA, Hennings H. Phenotypic expression of epidermal cells in vitro: a review. J Invest Dermatol 1983; 81 (1 Suppl): 11s-24s.
 
21.
Kligman LH, Akin FJ, Kligman AM. The contributions of UVA and UVB to connective tissue damage in hairless mice. J Invest Dermatol 1985; 84: 272-6.
 
22.
Kligman LH, Kligman AM. The effect on rhino mouse skin of agents which influence keratinization and exfoliation. J Invest Dermatol 1979; 73: 354-8.
 
23.
Montagna W, Chase H, Melaragno H. The skin of hairless mice. I. The formation of cysts and the distribution of lipids. J Invest Dermatol 1952; 19: 83-94.
 
24.
Sueki H, Gammal C, Kudoh K, Kligman AM. Hairless guinea pig skin: anatomical basis for studies of cutaneous biology. Eur J Dermatol 2000; 10: 357-64.
 
25.
Mackenzie IC. Ordered structure of the epidermis. J Invest Dermatol 1975; 65: 45-51.
 
26.
Bohling MW, Henderson RA, Swaim SF, Kincaid SA, Wright JC. Comparison of the role of the subcutaneous tissues in cutaneous wound healing in the dog and cat. Vet Surg 2006; 35: 3-14.
 
27.
Metcalfe DD, Kaliner M, Donlon MA. The mast cell. Crit Rev Immunol 1981; 3: 23-74.
 
28.
Lavker RM, Sun TT. Heterogeneity in epidermal basal keratinocytes: morphological and functional correlations. Science 1982; 215: 1239-41.
 
29.
Lavker RM, Sun TT. Epidermal stem cells. J Invest Dermatol 1983; 81 (1 Suppl): 121s-7s.
 
30.
Horie M, Sekiya I, Nakamura T, et al. In vivo pharmacokinetics of ketoprofen after patch application in the Mexican hairless pig. Biopharm Drug Dispos 2009; 30: 204-8.
 
31.
Lavker RM, Dong G, Zheng PS, Murphy GF. Hairless micropig skin. A novel model for studies of cutaneous biology. Am J Pathol 1991; 138: 687-97.
 
32.
Ichihara G, Katsumata Y, Moriyama H, et al. Pharmacokinetics of hydrogen after ingesting a hydrogen-rich solution: a study in pigs. Heliyon 2021; 7: e08359.
 
33.
Sano M, Shirakawa K, Katsumata Y, Ichihara G, Kobayashi E. Low-flow nasal cannula hydrogen therapy. J Clin Med Res 2020; 12: 674-80.
 
34.
Bajgai J, Lee KJ, Rahman MH, Fadriquela A, Kim CS. Role of molecular hydrogen in skin diseases and its impact in beauty. Curr Pharm Des 2021; 27: 737-46.
 
35.
Sano M, Ichihara G, Katsumata Y, et al. Pharmacokinetics of a single inhalation of hydrogen gas in pigs. PLoS One 2020; 15: e0234626.
 
ISSN:2451-0637
Journals System - logo
Scroll to top