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Research Article
COMPARATIVE ASSESSMENT OF ACUTE TOXICITY OF VINCANIN
HYDROCHLORIDE DERIVATIVES IN RESEARCH CONDITIONS
Submission Date:
October 01, 2022,
Accepted Date:
October 07, 2022,
Published Date:
October 18, 2022
Crossref doi:
https://doi.org/10.37547/ijmscr/Volume02Issue10-03
Yu.R. Mirzaev
Candidate Of Medical Sciences, Senior Scientific Researcher At The S.Yu. Yunusov Institute Of Plant Chemistry
Of The Academy Of Sciences Of The Republic Of Uzbekistan
T.T. Khamroev
Basic Doctoral Student Of The Institute Of Plant Chemistry Named After S.Yu. Yunusov Of The Academy Of
Sciences Of The Republic Of Uzbekistan
E.M. Ruzimov
Junior Scientific Researcher At The S.Y. Yunusov Institute Of Plant Chemistry Of The Academy Of Sciences Of
The Republic Of Uzbekistan
B.N. Khamdamov
Basic Doctoral Student Of The Institute Of Plant Chemistry Named After S.Yu. Yunusov Of The Academy Of
Sciences Of The Republic Of Uzbekistan
B.B. Abduazimov
Senior Scientific Researcher At The S.Yu. Yunusov Institute Of Plant Chemistry Of The Academy Of Sciences Of
The Republic Of Uzbekistan
Sh.M. Adizov
Phd, Senior Scientific Researcher At The S.Yu. Yunusov Institute Of Plant Chemistry Of The Academy Of
Sciences Of The Republic Of Uzbekistan
P.Kh. Yuldashev
Ds Doctor Of Chemical Sciences, Professor At The S.Yu. Yunusov Institute Of Plant Chemistry Of The Academy
Of Sciences Of The Republic Of Uzbekistan
B.J.Elmuradov
Ds Doctor Of Chemical Sciences, Professor At The S.Yu. Yunusov Institute Of Plant Chemistry Of The Academy
Of Sciences Of The Republic Of Uzbekistan
Journal
Website:
https://theusajournals.
com/index.php/ijmscr
Copyright:
Original
content from this work
may be used under the
terms of the creative
commons
attributes
4.0 licence.
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ABSTRACT
This research paper presents the isolation of norfluorocurarine alkaloids from the Vinca erecta plant, substances with
different chemical structures and the study of toxicological properties in various types of animals. Experiments have
shown that mice are more resistant to the effects of pyrazoline chloride and pyrazoline iodide than rats. From the
conducted studies, it can be concluded that it is advisable to carry out the biological activity of the studied substances
to rats that are relatively immune to the action of these substances and this will allow further use of dosages that are
relatively harmless to humans in various pathologies.
KEYWORDS
Acute toxicity, pyrazoline chloride, pyrazoline iodine methylate, intraperitoneal, Average lethal dose (LD50)
INTRODUCTION
In medical practice, the synthesis of new biologically
active substances to create new medicines with
valuable properties for the treatment and prevention
of various diseases is one of the most important tasks
of modern organic, bioorganic and medical chemistry,
as well as pharmacology. At the present stage of
intensive development of the pharmaceutical industry,
there are a number of successes in the chemical
synthesis of new compounds that are the basis for the
production of new drugs with high pharmacological
activity. Despite these successes, well-known drugs
used for the prevention and treatment of a number of
pathological conditions have low activity or lack of
effectiveness, as well as the presence of adverse
reactions that cause unpleasant sensations in patients
during treatment. The problem of finding new
substances with high pharmacological efficiency has
not lost its importance and relevance to this day [1-3].
In this regard, at the Institute of Chemistry of Plant
Substances named after S.Yu Yunusova Academy of
Sciences of the Republic of Uzbekistan has been
conducting large-scale research work on the isolation
and study of various biological activity of plant and
synthetic substances for many years. Currently,
scientific and practical work is underway on the
widespread use of these extracted substances not only
for pharmaceutical and medical applications, but also
as chemical and bioreactive substances for
experimental research. In the course of these works,
the outstanding scientist Professor P.X. Yuldashev,
senior researcher B.B. Abduazimov and other scientists
are conducting extensive work on the isolation of
norflorocurarine alkaloids from the Vinca erecta plant,
substances with different chemical structures.
Currently, a number of scientific studies are being
conducted on the pharmacotoxicological properties of
these alkaloids in relation to their acute toxicity and
antitumor activity [4-11].
The purpose of the study. Evaluation and comparison
of species sensitivity of vincanine hydrochloride
derivatives in various experimental animals
Materials and methods of research. The studies were
carried out on mongrel laboratory white mice weighing
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18-22 g and white rats weighing 150-180 g, kept in
standard vivarium conditions for 14 days and the
studied ones were carried out in accordance with the
methods set out in methodological, training manuals
and manuals [12-15]. In studies conducted on acute
toxicity, the studied substances were administered to
experimental animals by various methods of
administration and all experiments with animals were
carried out in accordance with the requirements of the
international recommendations of the European
Convention for the Protection of Vertebrates [16]. The
studied substances were administered by various
routes of administration, from low doses to doses
causing death, in all animals in the experimental group.
At the same time, all signs that occurred before death
in experimental animals exposed to substances were
recorded within 14 days. To determine the parameters
of "acute" toxicity, the Litchfield and Wilcoxon method
was used, and statistical processing of the results
obtained was carried out by the tabular method
proposed by R.B. Strelkov [17-18].
Results and their discussion. 1. Evaluation study of
acute toxicity of the substance pyrosaline chloride and
pyrosaline iodide when administered orally. The
general effect and "acute" toxicity of the substance of
the preparations pyrosaline chloride and pyrosaline
iodide were determined in mice and rats with a single
oral administration in various doses. Each dose of the
substance was studied on 6 animals. The observation
was conducted for 14 days.
To determine the parameters of "acute" toxicity, the
Litchfield and Wilcoxon method was used [17]. When
the substance pyrosaline chloride was administered
orally to mice and rats in small doses, the general
condition and behavior of the animals did not differ
from intact animals. Grooming was observed in the
studied large doses of pyrosaline chloride, after 5 to 10
minutes, depending on the doses, muscle weakness
appeared, manifested in the form of periodic lying on
the stomach and rare movements on the table surface.
During the study, after 30 minutes, the animals react to
external stimuli, but pain sensitivity to gentle pinching
of the tail root is preserved, weakness is visible, and
after 60 minutes, disorientation in space is sometimes
noticeable, repeated 2
–
3 times repeated sluggish
clonic convulsions, lateral position, slowing down and
stopping breathing. In the conducted studies, the
acute toxicity of pyrosaline chloride was LD50 = 550
(482.4-792) mg/kg in mice and LD50 = 420 (381.3-471.4)
mg/kg in rats (Table - 1).
Table
–
1. Comparison of acute toxicity of pyrosaline chloride when administered orally in mice and rats.
Name
of the substance
With oral administration
Attitude to the
toxicity of the
substances
under study
Types of animals
mice
rats
Pyrazoline Chloride
550 (482.4÷792) mg/kg
420 (381.3÷471.4) mg/kg
1,31
Note.P≤0.05
comparison with the control group
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Symptoms of poisoning caused by pyrazolone chloride
were similar in mice and rats, and only mice showed
resistance up to 1.31 times compared to rats.
In the conducted studies, when the substance
pyrosaline chloride was administered orally to mice
and rats in doses in small doses, the general condition
and behavior of animals did not differ from intact
animals as if it were pyrazoline iodine methylate. The
symptoms of poisoning caused by a substance that
was also studied in high doses are similar to the
symptoms of pyrazoline chloride poisoning, but death
from exposure to pyrazoline iodine methylate
occurred in a very short period of time, that is, within
30-35 minutes after the administration of the
substances under study. The data obtained as a result
of the studies are presented in table 2 below.
Table
–
2. Comparison of acute toxicity of pyrazoline iodine methylate when administered orally in mice and rats.
Name
of the substance
With oral administration
Attitude to the
toxicity of the
substances
under study
Types of animals
mice
mice
Pyrazoline iodine
methylate
1320 (1056÷1650)
mg/kg
813 (765.2÷911.5) mg/kg
1,62
Note.P≤0.05 comparison with the control group
The results of the studies showed that the symptoms
of poisoning caused by pyrazoline iodine methylate
were similar in mice and rats, and only mice showed
resistance up to 1.62 times compared to rats.
2. Evaluation study of acute toxicity of the substance
pyrazoline chloride and pyrosaline iodide when
administered intraperitoneally.
With oral administration of the substance pyrazoline
chloride and pyrazoline iodide to mice and rats in small
doses, the general condition and behavior of animals
did not differ from intact animals. An increase in the
dose
caused
inactivity,
increased
breathing,
"bunching". This condition lasted for 30-40 minutes,
according to the doses. When the drugs were
administered in these doses, the animals retracted
their stomachs. These phenomena disappeared after
10-15 minutes. The death of mice occurred during the
day in a dose of large doses. The average lethal dose
(LD50) with a single intraperitoneal administration of
the substance of the preparations pyrosaline chloride
and pyrosaline iodide in mice was 350 (270-490) mg/kg
and 128.4 (105.1-131.5) mg/kg, respectively, in rats 129
(115.2-171.5) mg/kg and 98.2 (87.6-106.2) mg/kg.
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Table
–
3. Comparison of acute toxicity of pyrosaline chloride and pyrazoline iodine methylate when administered
orally in mice and rats.
Name
of the substance
With intraperitoneal administration
Attitude to the
toxicity of the
substances
under study
Types of animals
mice
mice
Pyrosaline chloride
350 (270÷490) мг/кг
129 (115.2÷171.5) мг/кг
2,71
Pyrazoline iodine
methylate
128,4 (105,1÷131,5) мг/кг
98,2 (87,6÷106,2) мг/кг
1,31
Note.P≤0.05 comparison with the control group
As can be seen, pyrosaline chloride and pyrosaline
iodide belong to low-toxic substances (class IV toxicity,
in which, with intraperitoneal administration, LD50
ranges from 350 (270-490) mg/kg to 128.4 (105.1-131.5)
mg /kg mg/kg in mice [12], however, pyrosaline chloride
and pyrosaline iodide are less toxic in rats as compared
to rats. Mice can withstand higher doses of pyrazoline
chloride and pyrazoline iodide than rats. Natural
alkaloids, due to their high toxic effect on the entire
div, in doses possible for use, cannot cause a high
biological effect.
CONCLUSIONS
Preclinical study of general toxicology, general
pharmacology, as well as specific toxicology allowed us
to draw the following conclusions.
As a result of the work carried out to determine the
acute toxicity of pyrazoline chloride and pyrosaline
iodide in various experimental animals, it was found
that when administered orally, it belongs to class IV of
low-toxic substances, the studied substances when
administered intraperitoneally belong to class III of
medium toxic according to the toxicity classification of
substances.
However, mice were found to be more resistant to
pyrazoline chloride and pyrazoline iodide than rats.
From the conducted studies, it can be concluded that
it is advisable to carry out the biological activity of the
studied substances to rats that are relatively immune
to the action of these substances and this will allow
further use of dosages that are relatively harmless to
humans in various pathologies.
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