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STUDIES OF THE ANTI-INFLAMMATORY ACTIVITY OF CELAGRIP IN
PREPUBERTARY RATS
A.Kh. Rakhmanov
1
, F.A. Kutlieva
2
1
Doctor of Medical Sciences, Researcher, Center for Biomedical Technologies, Tashkent
Medical Academy,
2
Assistant, Department of Normal and Pathological Physiology, Urgensk Branch, Tashkent
Medical Academy, Tashkent, Uzbekistan
Abstract:
To identify the antiphlogistic activity of CelAgrip on the model of aseptic
inflammation induced by dextran, a study was conducted on growing animals of the
prepubertal period. It was found that CelAgrip has a distinct anti-inflammatory effect on the
model of acute inflammation induced by dextran. In its pharmacological activity, CelAgrip
is slightly superior to the well-known non-steroidal anti-inflammatory drug - Ibuprofen.
Key words:
aseptic inflammation, dextran, CelAgrip, Ibuprofen.
Conflict of interest.
The authors declare no obvious or potential interests related to the
publication of this article
Introduction.
Today, nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used worldwide to treat
various pathologies in the genesis of which inflammation occupies a leading place. However,
despite sufficient evidence of the beneficial effects of NSAIDs on children and adolescents,
there are no comprehensive data on infants. Various NSAIDs are used in infants: ibuprofen,
dexibuprofen, ketoprofen, flurbiprofen, naproxen, diclofenac, ketorolac, indomethacin,
niflumic acid, meloxicam, celecoxib, parecoxib, rofecoxib, acetylsalicylic acid and
nimesulide [1, 2]. NSAIDs have been shown to be effective for a variety of conditions such
as inflammation, fever and pain, and are also the mainstay of anti-inflammatory treatment,
for example, in childhood inflammatory rheumatic diseases [3-6]. It is known that limited
data are available on the safety of most NSAIDs for infants. Adverse drug reactions may be
renal, gastrointestinal, hematological or immunological, etc. [7-11]. Since NSAIDs are
among the most commonly used drugs in the pediatric population, safety and efficacy
studies can be conducted in routine clinical practice even in small infants. To increase the
safety of NSAIDs in infants, treatment should be initiated with the minimum dose
appropriate for age or weight. The duration of treatment and the amount of drug used should
be regularly assessed, and maximum dose limits and other recommendations of the
manufacturer or expert committees should be observed. Treatment of non-chronic conditions
such as fever and acute (postoperative) pain should be as short as possible. In this regard, the
development and creation of new less toxic and more effective antifungal drugs is of great
interest. The aim of this experimental study was to evaluate the anti-inflammatory activity of
CelAgrip in prepubertal rats.
Materials and research methods.
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Experimental studies were conducted on two month-old rat pups of both sexes weighing 75-
90 g. Before the experiment, all laboratory animals were carefully examined, weighed, their
age and motor activity were taken into account. During the entire preparation period for the
experiment, the laboratory animals were kept in a vivarium at a temperature of 20-25 ° C,
humidity of at least 50%, in a well-ventilated room and day / night light mode, in standard
plastic cages with 6 individuals in each, with a standard diet, the daily requirement is
compiled in accordance with the age of the animals. All laboratory animals participating in
the experiment before the experiment had a healthy appearance and were active.
Inflammatory edema of the paw in rats was modeled by subplantar administration of dextran,
which is widely used to assess the anti-inflammatory activity of new potential drugs [12, 13].
Experimental models of aseptic arthritis were reproduced by subplantar injection of 0.1 ml
of 6% aqueous dextran solution into the hind paw of rats. The prophylactic effect of
CelAgrip at a dose of 10 mg/kg was studied in comparison with the "gold standard"
Ibuprofen - 10 mg/kg [14]. The above-mentioned drugs were preventively administered
intragastrically with a metal tube 1 hour before the introduction of phlogogen. The paw
volume of the animals was measured using a plethysmometer (Ugo Basile Srl, Italy) [13]
before and 1, 2, 3 and 4 hours after the introduction of phlogogen. The increase in limb
volume and the index of inflammation inhibition were used as criteria for assessing the anti-
inflammatory efficacy [15,16]. The increase in paw edema was calculated using the formula:
P = O - I / I x 100,
where, P is the increase in paw edema by the hour; O – paw volume after administration of
the inflammation inducer;
I – paw volume before administration of the inflammation inducer.
The degree of inflammation inhibition was calculated using the formula:
100% - [O – I / I(O)÷ O – I / I(C)] x 100,
where, O – experimental animals (treated);
C – control group (without treatment)
The experiments were conducted in accordance with the “Rules for conducting work using
experimental animals”, as well as the rules adopted in the European Convention for the
Protection of Vertebrate Animals used for experimental research or other scientific purposes
(ETS No. 123, Strasbourg, 18.03.1986).
The obtained results of the experimental studies were processed statistically using the
standard software package StatPlus 2009 by well-known methods of variation statistics with
an assessment of the significance of indicators (M±m) and differences in the samples under
consideration by Student's t-test. A difference at a probability level of 95% or more (P<0.05)
was considered reliable.
Research results and their discussions
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Inflammation as a central link in the pathogenesis of many human pathologies is an urgent
problem of modern medicine, because despite the introduction of a huge number of drugs of
steroid and non-steroid structure in the treatment of inflammatory diseases, especially
chronic ones, it is a large, unsolved problem. In this regard, pharmacologists are faced with
the task of creating new effective drugs with a different mechanism of anti-inflammatory
action. Therefore, in-depth studies of drugs from other groups of drugs could solve the
problem of creating new anti-inflammatory drugs. According to the requirements of
preclinical studies of new drugs, anti-inflammatory properties should be tested in an
experiment on models of inflammation induced by various phlogogens. The results of the
studies showed that with subplantar administration of dextran, statistically significant
swelling of the paws was observed in animals in all groups, indicating the development of
inflammation. In the group of animals preventively receiving CelAgrip and Ibuprofen, a
certain modeling effect on the exudation process during aseptic inflammation was noted.
Thus, if in control rats after subplantar administration of dextran the paw volume increases
after 1 hour by 137.0%, after 2 hours - by 120.3%, after 3 hours - by 107.4% and after 4
hours - by 96.2% from the beginning of the experiment, then in rats receiving CelAgrip at a
dose of 10 mg / kg it was 89.1, 74.5, 63.6 and 52.7%, respectively. It is evident that under
the influence of CelAgrip the increase in the paw volume of rats was less than in the control.
At the same time, the degree of inflammation inhibition at the indicated study times was
35.0, 38.3, 41.1 and 44.8%, respectively. A classic representative of non-steroidal anti-
inflammatory drugs – ibuprofen in a similar dose – 10 mg/kg statistically significantly
suppressed the exudative phase of inflammation induced by dextran and its degree of
inflammation inhibition was 29.9, 32.5, 33.6 and 37.5%, respectively, in the above-studied
hours (Table 1). It should be noted that the anti-inflammatory effect of CelAgrip, although
higher compared to Ibuprofen, however these indicators between the groups were
statistically insignificant.
Table 1
Indices of anti-inflammatory activity of CelAgrip and Ibuprofen in the model of acute
exudative inflammation in prepubertal rats
Groups
Volume of paws, cm3
Increase
in
edema, %
Inflammation
inhibition,%
Before dextran
administration
1
hour
after
administration
of
dextran
Control
0,54 ± 0,02
1,28 ± 0,08
*
137,0
-
CelAgrip
0,55 ± 0,02
1,04 ± 0,10
*
89,1
35,0
Ibuprofen
0,53 ± 0,02
1,03 ± 0,07
*
94,3
30,9
Note: * -
reliable difference in relation to the original corresponding groups
Thus, CelAgrip and Ibuprofen in experimental animals have an anti-flagogenic effect
manifested in a decrease in the exudation process on the effect of dextran
References
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:7
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9
1.Ziesenitz VC, Welzel T, van Dyk M, Saur P, Gorenflo M, van den Anker JN. Efficacy and
Safety of NSAIDs in Infants: A Comprehensive Review of the Literature of the Past 20
Years. Paediatr Drugs. 2022 Nov;24(6):603-655. doi: 10.1007/s40272-022-00514-1.
2. Małgorzata Wisłowska. Juvenile Idiopathic Arthritis and Acute Rheumatic Fever,
Diagnosis
and
Treatment
in
Rheumatology
(2018):50-66.
https://doi.org/10.2174/9781681086552118010006
3.Денисова Р.В. Место ибупрофена в терапии боли у детей.
Вопросы современной
педиатрии /2012/ том 11/ № 1.С.46-50;
4.Ерофеева С.Б. Нестероидные противовоспалительные средства в педиатрической
практике: обзор эффективности и безопасности. Фарматека для практикующих врачей.
2012.Ns2-12. C.48-52;
5.
Victoria C. Ziesenitz., · Tatjana Welzel., · Madelé van Dyk. et al. · Efcacy and Safety
of NSAIDs in Infants: A Comprehensive Review of the Literature of the Past 20 Years.
Pediatric Drugs. Review article: Accepted: 25 April 2022.
https://doi.org/10.1007/s40272-
6.
Djanayev, G. Y. "Dorivor o ‘simliklar quruq ekstraktining rezerpinli me'da yarasiga ta'siri:
дис."
Tibbiyotdagi zamonaviy ilmiy tadqiqotlar
(2022).
7.
Шестаков Н.В., Пятигорская Н.В. Нестероидные противовоспалительные средства
при скелетно-мышечных болях: преимущества трансдермальных терапевтических
систем. РМЖ. 2019; 4:28–31.
8.Яковлев Е.В., Живолупов С.А., Гневышев Е.Н., Ветрова Т.В. Общая характеристика
и особенности применения нестероидных противовоспалительных препаратов при
лечении дорсопатий в клинической практике (обзор литературы). Медицинский совет.
2022;16(23):68–77.
https://doi.org/10.21518/2079-701X-2022-16-23-68-77
.;
9. Djanaev, G. Yu, et al. "Pharmacotherapy of Gastropathy (Literature Review)."
Texas Journal
of Medical Science
17 (2023): 67-76.
10.Ghlichloo I, Gerriets V. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) [Updated
2023 May 1]. - Available from:
https://www.ncbi.nlm.nih.gov /books/ NBK547742/
11. Khakimov, Z. Z., and G. Yu Djanaev. "Askarov OO Study Of the Effect of a Mixture of
Extracts of Medicinal Plants on the State of the Gastric Mucosa in Gastropathy Induced by
Indomethacin."
Eurasian Medical Research Periodical
19 (2023): 90-95.
12. Khakimov Z.Z., Rakhmanov A.Kh., Bekova N.B., Shukurlaev K.Sh. Specific features
of exudative and proliferative phase of inflammation when using calcium channel blockers.
American Journal of Medicine and Medical Sciences 2020, 10(10): 817-821.
Vo
lu
m
e
5,
M
ar
ch
,2
02
5
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
13.Khakimov Z.Z., Rakhmanov A.H. Some aspects of the mechanism of antiphlogenic
action of the Phytocomposition “Lesbohol”. International journal of medical sciences. ISSN:
2692-5206. www.academicpublishers.org Volume 5, March, 2025, Р.75-84.
14. Прохорович Е.А. Нестероидные противовоспалительные препараты — собрание
клонов или содружество ярких индивидуальностей? Взгляд клинического
фармаколога. РМЖ. 2020; 6:2–9.
15. Хакимов, З., Г. Джанаев, and Ж. Холматов. "Прокинетическая активность нового
фитопрепарата «Лесбохол»."
Евразийский журнал медицинских и естественных
наук
2.13 (2022): 205-209.
16. Воронков А.В., Лужнова С.А., Кодониди И.П. и соавтор. Сравнительный анализ
противовоспалительного
и
анальгетического
действия
ациклического
предшественника 1,3- Диазинона-4 соединения пятd1 и препарата Дапсон. Вестник
ВолгГМУ.2020;2(74):109-113.
