https://ijmri.de/index.php/jmsi
volume 4, issue 4, 2025
908
EXPERIMENTAL STUDY OF THE EFFECTIVENESS OF THE SUPRAMOLECULAR
COMPOUND OF METHYLENE BLUE AND HYDROXYPROPYL BETA-
CYCLODEXTRIN IN CARBON MONOXIDE POISONING
Sh.O.Xolliyeva, S.A.Saidov, J.A.Mirsultonov
Pharmaceutical Education and Research
Institute, Tashkent, Republic of Uzbekistan
Annotation:
This article presents the results of laboratory testing of the antidote properties of the
supramolecular compound methylene blue and hydroxypropyl beta-cyclodextrin for carbon
monoxide poisoning.
Keywords:
Methylene blue (MB), carbon monoxide (CO), cyanide and nitrate poisoning,
laboratory rat, hemoglobin, carboxyhemoglobin, effective antidote.
Introduction.
According to statistics, carbon monoxide poisoning is the second leading cause of death in the
world after alcohol poisoning. According to the Ministry of Emergency Situations, in Uzbekistan
in 2021, 125 people died from carbon monoxide poisoning, 115 were injured, and in 2022 this
figure reached 146 deaths and more than 50 injuries. Since the beginning of 2024, a total of 74
gas-related incidents have occurred in Uzbekistan (86 in 2023), resulting in 82 deaths and 80
injuries of varying degrees. In some cases, entire family members have died from carbon
monoxide poisoning due to a faulty chimney. As can be seen from the above, carbon monoxide
poisoning is common among the population, but unfortunately, these cases often end tragically.
Main part
Let's briefly talk about what carbon monoxide poisoning is and how the gas is formed. Carbon
monoxide is a strong poison, because it forms strong complexes with biologically active
molecules containing metal atoms (blood proteins, hemoglobin), which disrupts the oxygen
supply of tissues. It especially affects the cells of the central nervous system. The binding of
carbon monoxide to the Fe atoms in the hemoglobin protein disrupts the formation of
oxyhemoglobin, which carries oxygen from the lungs to the tissues. Even if there is 0.1% CO gas
in the air, this gas displaces half of the oxygen from oxyhemoglobin. In such cases, even the
presence of a large amount of pure oxygen in the air cannot prevent death from asphyxiation.
The daily permissible dose of carbon monoxide in atmospheric air is set at 3 mg / m³. In many
places in the workplace and public transport, it is 20 mg / m³. This gas is released into the air as
part of volcanic and swamp gases, and by the secretions of plankton and other microorganisms.
Thus, 220 million tons of CO are released into the atmosphere from the surface layers of the
ocean every year. In addition, large amounts of carbon monoxide are released into the air from
coal mines and forest fires. 300.4 thousand tons of CO are also released during the smelting of
every million tons of steel. In total, the annual release of man-made CO into the air is 600
million tons.
Based on the above, it is very important to develop alternative medical treatments for patients
with carbon monoxide poisoning. Traditional treatment methods (hyperbaric oxygen therapy) are
expensive and have limitations in providing rapid relief. Methylene blue (MK) converts COHb to
normal Hb, but its toxicity and low solubility limit its clinical application. In this study, the
antidote properties of the supramolecular compound MK+HP-β-CD were experimentally
investigated.
Research methods used based on the comments.
https://ijmri.de/index.php/jmsi
volume 4, issue 4, 2025
909
Experimental group:
12 healthy male rats (Sprague-Dawley yoki Wistar)
Experimental group (n=6):
Lung saturation was measured and recorded using a specialized
veterinary Berry AM6200 Capnograph pulse oximeter for animals administered CO poisoning +
MB+HP-β-CD solution.
Control group (n=6):
Animals exposed to CO poisoning + saline were monitored for pulmonary
saturation using a Berry AM6200 Capnograph pulse oximeter. The duration of the experiment
was 1 day. Before the start of the experiment, the laboratory rats were named and their weight
was measured and recorded using an analytical scale. A special animal-safe alcohol-based
yellow dye was used to clearly distinguish the laboratory rats. The dye was used to label the rats'
tail, head, spine, left leg, left arm, right leg, right arm, left and right flanks, and neck. The Berry
AM6200 Capnograph was used and saturation and pulse were determined for 5 minutes, 1, 3, 6,
12, and 24 hours. 5 minutes after the animals were exposed to carbon monoxide, the pulse and
saturation of the animals in the control group did not differ from the experimental group. One
hour after poisoning the animals with carbon monoxide, the saturation in the experimental
animals was 10% higher and the pulse rate was 8% higher than in the control group. After 3
hours, the saturation was 20% higher and the pulse rate was 12%. 24 hours after poisoning the
animals and the introduction of 0.5% methylene blue, the saturation was on average 90%, the
pulse rate was 100 beats per minute. Compared with the results of the animals in the control
group, the saturation in the experimental group was restored faster, the pulse rate was within
normal limits. The result shows that the injection of 0.5% methylene blue saturates the blood
with oxygen and relieves the div from carbon monoxide poisoning.
Lung saturation and pulse in animals that received the poisoned injection and those that
did not.
Time after poisoning.
5 min
1 hour
3 hour
24 hour
№ Name
weight SpO2 % /
PR/bPm
SpO2 % /
PR/bPm
SpO2 % /
PR/bPm
SpO2 % /
PR/bPm
Ex
pe
rim
en
ta
lg
ro
up
(in
je
ct
ed
)
1
Head
215
40/40
48/127
69/110
93/127
2
Neck
225
39/25
51/89
67/98
89/143
3
spine
200
35/64
61/134
73/107
96/138
4
waist
220
36/56
57/118
76/113
87/146
5
Left hand
195
35/48
54/113
64/107
90/131
6
Right hand 225
38/58
59/121
79/126
91/118
Co
nt
ro
l
gr
ou
p
(n
o
in
je
ct
io
n)
7
Left hand
210
36/46
41/146
57/158
Death
recorded
8
Right foot 185
35/50
Death
recorded
-
-
9
Left
215
39/58
43/134
55/146
67/114
https://ijmri.de/index.php/jmsi
volume 4, issue 4, 2025
910
Conclusions and results.
The supramolecular compound MK+HP-β-CD is an effective antidote
for CO poisoning, restoring SpO₂ to 90% within 24 hours.
HP-β-CD increases the solubility of MK and reduces its toxicity. The results can serve as a basis
for clinical trials. By studying the changes occurring in the div and analyzing them in depth, it
will be possible to develop alternative treatment methods for carbon monoxide poisoning.
References
.
1.
WHO. (2021). Carbon Monoxide Poisoning: Clinical
Management.
2.
Thom, S.R. (2011). Am J Physiol, 301(6), H1784-H1792.
3.
OʻzR Sogʻliqni Saqlash Vazirligi. (2024). Zaharlanish
Holatlari Hisoboti.
4.
Yangi
farmakologik
moddalarni
eksperimental
(klinikgacha) o'rganish bo'yicha uslubiy ko'rsatmalar. Rossiya Tibbiyot fanlari akademiyasining
muxbir aʼzosi, professor R. U. XABRIEVning umumiy tahriri ostida. Ikkinchi nashr, qayta ko'rib
chiqilgan va kengaytirilgan. M.: - 2005. - M.: "Nashriyot" OAJ "Tibbiyot", 2005. - 830 b.
5.
Belenkiy M.L. Farmakologik ta'sirni miqdoriy baholash
elementlari. L Medgiz 1963, -152 b.
6.
Ryaxovskiy
Andrey
Evgenievich
’’Alkogollik
intoksikasiyasi fonida kalamushlarni is gazi bilan zaharlanishni organizmda morfofunksional
o’zgarishi’’ Rossiya Federatsiyasi Sog'liqni saqlash vazirligining "Bashkir davlat tibbiyot
universiteti
7.
Novelli, P. C. (1999). CO in the atmosphere: measurement
techniques and related issues. Chemosphere — Global Change Science, 1(1-3), 115—126,
https://doi.org/10.1016/S1465-9972(99)00013-6
8.
Changes of Nuclear Factor Kappa-B Pathway Activity in
Hippocampus After Acute Carbon Monoxide Poisoning and Its Role in Nerve Cell Injury.
9.
Changes of Nuclear Factor Kappa-B Pathway Activity in
Hippocampus After Acute Carbon Monoxide Poisoning and Its Role in Nerve Cell Injury.
buttock
10 Right
buttock
195
42/68
47/145
58/183
69/135
11 Head/back 230
35/54
39/137
Death
recorded
-
12 Head/spine 210
39/56
45/87
61/114
73/156
