The document discusses hormoligos, a new approach to understanding the mechanism of action of medical gases like hydrogen, ozone, and xenon. It summarizes that these gases have almost identical pharmacological effects despite different chemical properties. This is explained by their ability to modulate the endocrine system and restore homeostasis. The gases are found to influence hormone levels like cortisol and aldosterone, suggesting hormone modulation underlies their therapeutic effects.

1. Hormoligos as a new approach to
understanding the mechanism of action of
medical gases using hydrogen, ozone, and
xenon as an example.
E.I.Nazarov
Asian-European Union of ozone therapists
In the last decade, a new direction has arisen and is actively developing -
the study of medical gases as a separate group of pharmacological
substances. Since 2011, the multidisciplinary journal Medical Gas
Research has been published devoted to the use of medical gases in
therapy.

2. The gases that are called “medical gasses” are Oxygen, Ozone, Hydrogen,
Monoxide and Carbon Dioxide, Hydrogen Sulfide, Carbon Disulfide, Nitrous
Oxide, Helium, Argon, Krypton, Xenon and Radon.
In this presentation, we consider three gases - an ozone as oxidizing agent, a
hydrogen as reducing agent, and an inert gas xenon. Surprisingly, these gases
have an almost identical spectrum of pharmacological activity. This is contrary
to the basic principles of pharmacology, in which the chemical properties of a
substance determine the pharmacological effect. Let's try to figure it out and
start with hydrogen.

3. CHART 2
HYDROGEN THERAPY

4. METHODS OF HYDROGEN
THERAPY
inhalation of 2-4%
hydrogen-air mixture.
Drinking saturated (1.6 ppm)
and superaturated (5-6 ppm) water
intravenous infusion of a
Saline saturated with
hydrogen (1.6 ppm)
AHT-H2 autohemotherapy
major with hydrogen 4

5. The pharmacological activity
of the molecular hydrogen in
animal models of
pathological conditions of
the body.
5

6. Drinking hydrogen water reduces liver obesity in the diabetic mouse line
and even reduces their size.
Molecular hydrogen improves obesity and diabetes by inducing hepatic
fibroblast growth factor 21 and stimulating energy metabolism in db/db
mice. Kamimura, N., Nishimaki, K., Ohsawa, I.,et al (2011). Obesity, 19(7), 1396-1403

7. Molecular hydrogen is protective against 6-hydroxydopamine-induced
nigrostriatal degeneration in a rat model of Parkinson's disease. Fu, Y., Ito,
M., Fujita, Y., Ito, M., Ichihara, M., Masuda, A., ... & Ohsawa, I. (2009). Neuroscience Letters, 453(2), 81-85
methamphetamine-
induced rotation test in
mice
6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of
Parkinson's disease is largely prevented by drinking hydrogen water. This
is seen on gistological slices of the Substance Nigra. Another model of
Parkinson's disease estimated on methamphetamine-induced, rotation
movement of mice is also prevented by hydrogen water.
7

8. Control Alcohol H2-Alcohol Alcohol+free access to H2Water
Alcohol treated with hydrogen under conditions of
reproduction of a model of chronic alcohol intoxication
causes a significant limitation of pathological metabolic
changes in laboratory rats.

9. On the left is the appearance of rats after a
month of alcohol intoxication. In the center - also
when intoxicated with alcohol saturated with
hydrogen, on the right - also with free access to
drinking water saturated with hydrogen.
Назаров Е.И., Дерюгина А.В., Иващенко М.Н.., Влияние
молекулярного водорода на активность печеночных маркеров,
Естесственные и технические науки. № 9 (135) 2019 г., стр. 87

10. The dynamics of the life span of rats under conditions
when the only source of water was tap water (blue curve),
water with a O2(red curve), water with H2(green curve).
The data are borrowed from [. Pavel D. Kolesnichenko et al. Natality and Mortality with
Reduced RED-OX Potential Drinking Water, Journal of International Pharmaceutical
Research, v 45, p 450-453].
H2 water
O2 water
Tap water

11. Some clinical data on the
therapeutic activity of
hydrogen
11

12. 12
A IV infusion of saline, saturated with hydrogen, reduces the
area, of infarction zone, of a brain stem stroke. Practically, in
ten days with hydrogen therapy , the specified parameter
decreases to a normal value.
Improved brain MRI indices, in the acute brain stem
infarct sites, treated with hydroxyl radical scavengers,
Edaravone and hydrogen, as compared to Edaravone
alone. Ono, H., Nishijima, Y., Adachi, N et al., 2011 Medical gas
research. – 2011. Т. 1. №. 1. С. 1

13. Hydrogen inhalation, prevents the deterioration ,of
the NIHSS index, which is used, to assess the
neurological outcome, and the degree of recovery,
in patients with stroke (level of consciousness,
sensory function, language, etc.).
The Barthel Index, (BI) - index of
independent living, also becomes more
stable, with hydrogen inhalations.
There is another study that, investigated the comparative activity of
Edvarone and hydrogen. The study, was conducted, on a group of 25
patients, who received inhalation, of 3% H2, for one hour, within 7 days.
.
13
Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A
Randomized Controlled Clinical Study on Safety and Neuroprotection.
H. Ono, Y. Nishijima at al. Journal of Stroke and Cerebrovascular Diseases, Vol. 26, No. 11
(November), 2017: pp 2587–2594

14. Total Unified Parkinson’s Disease Rating Scale (UPDRS) scores in the H2-water group (n=9) improved
(median, -1.0; mean +- standard deviation, -5.7+-8.4), whereas UPDRS scores in the placebo group (n=8)
worsened (median, +4.5; mean+-standard deviation, 4.1+-9.2)
Drinking hydrogen water, in the amount of two liters per day, for one
year, causes the reverse development, of symptoms of Parkinson's
disease.
14
Pilot study of H2 therapy in Parkinson's disease: A
randomized double‐blind placebo‐controlled trial.
Yoritaka A. et al. Movement Disorders. – 2013. – Т. 28. – №. 6. – С. 836-
839.

15. Drinking water, saturated with hydrogen is useful, in the prevention of
diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). Patients
consumed 900 ml hydrogen water a day, or 900 ml of simple water,
(placebo) for 8 weeks. It can be seen from the slide, drinking hydrogen
water, shifts the average glucose level, for a group, below the upper
level of norm.
Supplementation of hydrogen-rich water, improves lipid and glucose
metabolism, in patients with type 2 diabetes, or impaired glucose
tolerance. Kajiyama S. et al. Nutrition Research. – 2008. – Т. 28. – №. 3. – С. 137-143.

16. Hydrogen baths, and intravenous infusions, of hydrogen-saturated
saline, are effective, in treating skin diseases. Two-months treatment,
with hydrogen baths, causes a 75%, decrease in the psoriasis severity
index. On the right, the result of the use of hydrogen droppers (400 ml,
1.6 ppm H2) in the treatment of acute herpetic inflammation, of the
skin, is shown.
Positive effects of hydrogen-water bathing in patients of psoriasis and
parapsoriasis en plaques . Zhu Q. et al. Scientific reports. – 2018. – Т. 8. – №. 1. – С.
8051.
Ono H, Nishijima Y, Adachi N, et al (2012): Hydrogen (H2) treatment for acute erythymatous skin
disease. A report of 4 patients with safety data and a non-controlled feasibility study with H2
concentration measurement on two volunteers. Med Gas Res, 2: 14. 16

17. First approach - Hydrogen is a
selective scavenger of radicals
17
We have seen above that molecular hydrogen is a very
effective therapeutic agent that surpasses the currently
available traditional medicine. However, what is the
mechanism of this activity?
There are two approaches to explaining the therapeutic effect
of molecular hydrogen. The first is well known to ozone
therapists. This approach explains all the therapeutic effects
of hydrogen with the antioxidant effect of the latter.

18. 18
At body temperature, hydrogen is a kinetically inert gas, and practically does not
participate, in the vast majority, of biochemical reactions. The reason for this inertness
is that, in order for hydrogen to react, for example, with oxygen, you need to raise the
temperature, to 550 degrees of Celsius. Therefore, earlier, molecular hydrogen, was
considered, as a biologically inert gas. The situation changed, since 2007, after the
pioneering work of Oshawa, and his coauthors. They revealed that, hydrogen can react
with hydroxyl and peroxynitrite radicals, at body temperature. As a result, these
dangerous radicals, are inactivated.

19. Molecular hydrogen, is a unique natural antioxidant. It is unique, because
hydrogen molecules, selectively intercept only dangerous hydroxyl, and
peroxynitrite radicals, practically, not suppressing the activity of “useful”
reactive oxygen forms (hydrogen peroxide, anion of superoxide radical, NO
radical, etc.). It is natural, because molecular hydrogen, is synthesized, by
intestinal microflora, in macrovolumes. Molecular hydrogen has, the
property of super-permeability, and it is rapidly distributed, by the blood
in the body, when administered orally, and rectally.
Compositi
on of
intestinal
gases
19

20. It is known that, the imbalance of oxidation and antioxidant reactions, is
the cause of most diseases. It is believed that, low doses of ozone,
activate the antioxidant system. It is also believed that, hydrogen
therapy, reduces the overall intensity, of oxidative processes. The final
result is, to restore the balance of oxidative-antioxidant reactions and,
consequently, improve the condition of the body, or health. This
approach, familiar to us from the theory of ozone therapy, emerged in
2007 and is used as a theoretical basis for hydrogen therapy to this day.
However, there is an increasing accumulation of facts that this simplified
method of interpretation is not as good as it seems.

21. For example, the neuroprotective effect of drinking hydrogen
water in a mouse model of Parkinson's disease persists for at
least three days after end of drinking of water.
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) - nerve poison kills dopaminergic neurons.
Pictures is borrowed from Noda, et al., Multiple Effects of Molecular Hydrogen and its Distinct MechanismJ Neurol Disord 2014, 2:6

22. Hydrogen water releases the hormone ghrelin from the walls of the
stomach. The hormone ghrelin secretes the growth factors of
dopaminergic neurons in the Substance of Nigra and thus has an
antiparkinsonian effect. The protective effect of hydrogen water is
removed by an ɓ1-adrenergic blocker, atenolol, which blocks the
increase in ghrelin concentration. The pictures is borrowed from Noda, M.,
Ohsawa, I., Ito, M., & Ohno, K. (2014). Beneficial effects of hydrogen in the CNS and a new brain-stomach
interaction. Eur J Neurodegener Dis, 3, 25-34

23. The proposed scheme is the stomach-brain interaction mediating the neuroprotective effect of
hydrogen-saturated water. The circuit is borrowed from Noda, M., Uemura, Y., Yoshii, Y., Horita, et al. (2019).
Circulating messenger for neuroprotection induced by molecular hydrogen. Canadian journal of physiology and
pharmacology, 97(10), 909-915.
This diagram illustrates the essence of the Second approach - mediation of the
effects of hydrogen by the endocrine system. What is the appeal of this
approach? The attractiveness lies in the assumption that molecular hydrogen
activate the neuro humoral system that underlies the homeostasis system.
Since the disease in the most general sense is a violation of homeostasis, the
restoration of homeostasis logically means the treatment of the disease,
regardless of the etiology. Thus, a wide spectrum of pharmacological activity of
hydrogen can be explained. However, does this hypothesis relate to other
gases, for example for Xenon?

24. Chart 2
Xenon therapy.
1

26. Pioneer of xenon in medicine.
Nikolai Vasilievich Lazarev, Russia (1895-1974)

27. Therapeutic properties of xenon
analgesic,
antispasmodic,
cardiotonic,
neuroprotective
antistress,
antihypoxic,
immunostimulating,
anti-inflammatory,
anabolic,
neurohumoral,
vasoplegic

28. Cell apoptosis. Immunofluorescence cortex M.Maize,2004
Xenon, even at very high anesthetic concentrations, does not cause
apoptosis of cortical neurons like ketamine or nitrous oxide, but even
protects neurons from non-toxic poisons.

29. Neuroprotective mechanism of xenon action is currently associated
with the inhibition of receptors of Glutamate (NDMA-receptors)

30. 0
10
20
30
40
50
60
70
80
90
100
0 5 10 45 100 450 1000
percentageofmaximumcurrent
throughthemembrane
Concentration of NMDA
+ Xenon
Control
CONTR
OL
+
XENON
NMD
A
NMDA
10 S
500pA
Franks et al. Nature, 396:324,
1998
This is proved in a direct experiment on measuring the ion currents of
a neuron membrane upon excitation of glutamate receptors.

31. Dynamics of biochemical and hormonal parameters
during xenon inhalation
In addition, it was found that xenon inhalations cause a
change in the hormonal status of organism. This is evident
from the sharp dynamics of growth hormone, cortisol, and
tereotropic hormones. Thus, the neurohumoral effect of
xenon can be considered proven.

32. Chart 3.
OZONE THERAPY

33. Does ozone therapy, affect the hormonal status of patients?
Yes, and it influences very strongly, and very peculiarly. On
slide the normalized level of Cortisol, in the blood of six
patients (41-64 years old) in control, during the course of
AHT-O3 procedures (dose 27μg/kg, every other day) and
within one months after completion of the course.
7
In slide, we see, that after the start of the course of autohemotherapy
with ozone, the oscillatory dynamics, of cortisol level starts. After the
completion of the course of procedures, the level of cortisol stabilizes,
at the reached level, for at least one month.

34. norm
Cortisol
This is a typical pattern, of cortisol level dynamics, during the real
course of ozone therapy treatment (AHT-O3,dose of ozone - 2 mg).
We see , that the initially inflated level of cortisol, unpredictably
changes, during the course of the procedures. Before the fifth
procedure, cortisol levels return to initially inflated level.
It is important, that the patient's well-being, improves after the first
procedure, and then, worsens again before the fifth procedure.
Thus, cortisol levels correlate with patient well-being

35. nor
m
aldosterone
Mineral corticoid levels, of this patient, vary even more. As a result,
cortisol and aldosterone are, in the upper half of norm. This, and
the previous graph, shows very clearly, the hormone modulating
effect of ozone. Indeed, if under the action of a pharmacological
factor, the concentration of a hormone, changes 10 times, then
why look for some other reasons for the therapeutic effect of this
factor?

36. Ozone are: anti-inflammatory - immune modulating, anti-microbial,
anti-viral and anti-hypoxic - vasodilatory cardio-protectors .......
detoxifying agent substance, with a therapeutic index of more than 350
times, and half-life of 60 days.
Adaptogens (examples - alkaloids of Rhodiola Rosea, Aloe
Vera, Ginseng Rauwolfia, etc. ) are: anti-inflammatory - immune
modulating, anti-microbial, anti-viral and anti-hypoxic - vasodilatory
cardio-protectors ....... detoxifying agent substance with a therapeutic
index of more than 350 times, and half-life of 60 days
What about classification of ozone as a
pharmacological agent? This is odd, but
there is no pharmacological classification
of ozone. We can only say that:
Does pharmacology know substances, with such a wide range of
therapeutic activity? Yes, these are adaptogens belonging to the group
of plant alkaloids.

37. Coincidence of the pharmacological characteristics,
of plant alkaloids and ozone, seems to us to be not
accidental, especially since ozone, and alkaloids are
potent poisons. In this regard, we propose to use the
concept of hormoligos, instead of the practically
empty concept of hormesis. The concept of
hormoligosis , from the Greek hormo - excitation,
oligo - small quantities, was offered by T. Luckey at
1975 in article Hormology with inorganic
compounds / T. D. Luckey, Environ. Qual. Saf. Suppl. -
1975. —N 1. - P. 81 - 103, 115 - 118. In this concept,
the action of toxicants in small doses, is associated
with hormone-like or hormone modulating action of
them.

38. A new approach to the therapeutic effect
of systemic ozone therapy or what gives
us the replacement of the concept of
hormesis to the concept of hormoligosis.
So, we have considered the problems, that occur, in the
modern theory and practice, of systemic ozone therapy. We
believe, that they can be solved by taking as a basis the
hormoligosis, instead of LP of membranes, in combination
with hormesis. Let me remind you, that the main thing in the
concept of hormoligosis, is that poisons in low
concentrations, cause hormonal shifts in the patient's
organism.

39. Synthesis scheme of prostaglandins, prostacyclins,
thromboxanes and leukotrienes, from arachidonic acid. As a
result of the synthesis of these aicosanoids , hydroperoxides
and malonic dialdehyde, which are usually considered to be
products of LP of membranes, are formed.

40. A new approach to the therapeutic effect of systemic ozone therapy or
what gives us the replacement of the concept of hormesis to the
concept of hormoligosis.
So, we have considered the problems, that occur, in the modern theory
and practice, of systemic ozone therapy. We believe, that they can be
solved by taking as a basis the hormoligosis, instead of LP of membranes,
in combination with hormesis.

41. Understanding that the systemic effect of medical gases relies on changes
in the hormonal balance allows the doctor to develop an individual
approach to the duration and intensity of the course of ozone therapy
based on data on the cardio intervalogram (see ozoneprotocols.org) , as
well as apply combined methods of treatment with medical gases, for
example, ozone-hydrogen therapy. At present Econika Engeneering,
produce equipment for ozone, ozone-hydrogen and xenon therapy.
Traditional ozone generators The world's first ozone-hydrogen Xenon machine
Bozon- family UV-photometric generator to receive ozone
tools and hydrogen from water

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Thanks for your attention
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