American Journal Of Biomedical Science & Pharmaceutical Innovation
5
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VOLUME
Vol.05 Issue01 2025
PAGE NO.
5-8
10.37547/ajbspi/Volume05Issue02-02
Analysis of models for involving experimental liver
poisoning in rats
Urazbayeva Sh.O.
Tashkent Pharmaceutical Institute, Uzbekistan
V.F. Tukhtasheva
Institute of Pharmaceutical Education and Research, Uzbekistan
Saidov S.A.
Institute of Pharmaceutical Education and Research, Uzbekistan
Yakubov A.K.
Institute of Pharmaceutical Education and Research, Uzbekistan
Received:
07 December 2024;
Accepted:
09 January 2025;
Published:
11 February 2025
Abstract:
In recent years, chronic liver diseases have become a significant cause of death and disability [2], there
is a trend towards an increase in the number of patients with chronic liver disease. It is widespread mainly among
people of working age [3], which is explained by the living conditions of modern humans and the presence of a
large number of chemical compounds in the environment. This leads to changes in metabolic processes in the
liver and its toxic damage.
According to WHO data, over the past 20 years, there has been a trend towards an increase in the number of liver
diseases leading to high mortality worldwide. Today, the number of patients with various hepatobiliary
pathologies in the world exceeds 2 billion people. In the CIS countries alone, between 500,000 and 1 million people
with various liver diseases are registered annually [4].
A sharp increase in the number of patients with chronic liver diseases was facilitated by an increase in the
incidence of viral and toxic (alcoholic and drug) hepatitis, as well as a significant increase in the number of patients
with obesity and diabetes mellitus.
The hepatoprotective properties of drugs improve metabolism, inhibit peroxidation, activate lipid metabolism,
and protect mitochondrial and microsomal enzymes from damage to varying degrees [1].
Keywords:
Hepatitis, experimental hepatitis, paracetamol hepatitis, hepatitis induced by 40% ethyl alcohol,
galactosamine hepatitis induction model, carbon tetrachloride (CCl4).
Introduction:
Today, despite the wide range of
preparations with hepatoprotective properties, the
demand for this group of preparations remains high.
Scientific research aimed at solving this problem is
based on the correct choice of the hepatitis model and
the correct conduct of the experiment. Therefore, we
began our research with the analysis of models of
experimental hepatitis induction.
Currently, the following methods are used in the study
of experimental liver poisoning:
1. Citing a model of carbon tetrachloride (CCl4)
poisoning in the liver
Calculating a model of liver poisoning using carbon
tetrachloride (CCl4) is a widely used method in
toxicological and biomedical research. When creating
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American Journal of Applied Science and Technology (ISSN: 2771-2745)
this model, the following steps are carried out:
Experiment design
For this purpose, groups are created for white male
laboratory rats. At least 4 groups are taken, with no less
than 6 white male laboratory rats in each. The 1st group
is the "intact" group, in which the disease is not caused.
The 2nd group is the "control" group, where carbon
tetrachloride (CCl4) causes liver poisoning and is not
treated. The 3rd group is the experimental group,
where carbon tetrachloride (CCl4) causes poisoning in
the liver, and before this, the studied drug was
administered in a certain dose. The 4th group is the
comparison group, where carbon tetrachloride (CCl4)
causes poisoning in the liver, and before this, the drug,
which is widely used in medical practice today, is
administered in a certain dose.
Experiment
These groups were cut 0.5 cm from the tip of the tail of
all laboratory rats, blood was taken to obtain
preliminary biochemical results, and a preliminary
analysis was conducted. After this, the "Intakt" group
was given distilled water for 6 days, corresponding to
div weight. The control group was also given distilled
water for 6 days. The experimental group was given the
studied drug at 1 mg/kg or at a certain dose for 6 days.
The comparison group is given a drug that has been
used in medical practice for 6 days. On the 7th day, all
groups, except the intact group, were administered
50% carbon tetrachloride (CCl4) 0.3 ml for every 100 g
of div weight 3 times a day. Blood was taken from the
tail of laboratory rats of all groups for biochemical
analysis.
Monitoring and evaluation
Monitoring for several hours or days after
administering the drug.
Researchers evaluate changes occurring in the liver,
blood enzyme levels, and other biological indicators.
This process helps to understand the mechanisms of
liver poisoning.
Health metrics
Observe the general health of rats, in particular their
activity and behavior.
`
Liver function assessment
Taking blood samples to assess liver function and
measuring ALT (alanine aminotransferase), AST
(aspartate aminotransferase), and bilirubin levels.
2. Eliciting a model of liver poisoning in laboratory rats
using paracetamol.
Citing a model of liver poisoning in laboratory rats using
paracetamol (acetaminophen) mainly uses the ability
of paracetamol to damage liver cells at high doses. This
model is widely used for the study of liver diseases and
the testing of new treatment methods. Below is the
process of creating a model of liver poisoning using
paracetamol:
Experiment design
For this, 180-220 g of laboratory rats (for example,
Sprague-Dawley or Wistar rats) are selected and
grouped. For this, at least 4 groups of white male
laboratory rats are taken, with no less than 6 in each.
The 1st group is the "intact" group, in which the disease
is not caused.
The 2nd group is the "control" group, where
paracetamol causes liver poisoning and is not treated.
The 3rd group was the experimental group, where
paracetamol induced liver poisoning, and the studied
drug was previously administered in a specific dose.
The 4th group is the comparison group, where
paracetamol causes liver poisoning, and before this,
the drug, which is widely used in medical practice
today, is administered in a certain dose.
Experiment
Before starting the experiments, the rats intended for
the experiment are weighed and grouped. Blood was
taken from all groups of rats and the initial biochemical
blood parameters were determined.
Modeling of liver damage using paracetamol was
carried out as follows: laboratory white male rats
weighing 180-220 g were given the studied preparation
at various doses once a day for 14 days.
For the next two days, 1000 mg/kg of paracetamol is
administered orally once.
- The rats of the control group were given distilled
water under the same conditions, and they were also
injected with paracetamol at 1000 mg/kg for the last 2
days.
The intact group is given distilled water under the same
conditions.
The drug of comparison (placebo or another drug) is
also administered for 14 days and paracetamol 1000
mg/kg once a day for the last 2 days.
Monitoring and evaluation
Monitoring for several hours or days after
administering the drug.
On the last day of the experiment, blood was taken
from all groups of laboratory rats, biochemical
indicators were analyzed, and the results were
evaluated by comparison with the initial blood test.
Health metrics
Observe the general health of rats, in particular their
activity and behavior.
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American Journal of Applied Science and Technology (ISSN: 2771-2745)
Liver function assessment
Taking blood samples to assess liver function and
measuring ALT (alanine aminotransferase), AST
(aspartate aminotransferase), and bilirubin levels.
Calculation of a liver poisoning model in laboratory rats
using 40% ethyl alcohol.
With the help of this model, it is possible to study the
mechanisms of ethanol leading to liver poisoning and
test potential antidotes or treatment methods.
Experiment design
For this purpose, groups are created for white male
laboratory rats. At least 4 groups are taken, with no less
than 6 white male laboratory rats in each. The 1st group
is the "intact" group, in which the disease is not caused.
The 2nd group is the "control" group, where poisoning
of the liver with 40% ethyl alcohol is induced and is not
treated. The 3rd group was the experimental group,
where poisoning of the liver was induced with 40%
ethyl alcohol, and before this, the studied drug was
administered in a certain dose. The 4th group is a
comparison group (placebo or another drug), in which
poisoning of the liver is induced with the help of 40%
ethyl alcohol, and before this, the drug, widely used
today in medical practice, is administered in a certain
dose.
Experiment
Before starting the experiments, the rats intended for
the experiment are weighed and grouped. Blood was
taken from all groups of rats and the initial biochemical
blood parameters were determined.
Modeling of liver damage using paracetamol was
carried out as follows: laboratory white male rats
weighing 180-220 g were given 40% ethyl alcohol 1
time a day for 7 days, 2 hours before administration, in
various doses.
On the last 7 days of the experiment, 40% ethyl alcohol
is administered orally once for 7 days, 2 hours before
administration.
- The rats of the control group were given distilled
water under the same conditions, and on the 7th day,
2 hours after the injection of distilled water, they were
also injected with 7 ml/kg of 40% ethyl alcohol using a
probe.
The intact group is given distilled water under the same
conditions.
The comparison drug (placebo or another drug) is also
administered for 7 days, and 7 ml/kg of 40% ethyl
alcohol is administered 2 hours after the last drug was
administered.
Monitoring and evaluation
Monitoring for several hours or days after
administering the drug.
On the last day of the experiment, blood was taken
from all groups of laboratory rats, biochemical
indicators were analyzed, and the results were
evaluated in comparison with the initial blood test.
Health metrics
Observe the general health of rats, in particular their
activities and behavior.
Liver function assessment
Taking blood samples to assess liver function and
measuring ALT (alanine aminotransferase), AST
(aspartate aminotransferase), and bilirubin levels.
3. Experimental model for inducing galactosamine
hepatitis
The galactosamine hepatitis induction model is a
widely used experimental method for studying liver
diseases. With the help of this model, it is possible to
study the processes of inflammation and liver damage.
This method is closest to viral liver disease
(Vengerovsky A.I. et al. 1999-2002). Below is
information about the process of creating a model of
galactosamine hepatitis:
In this method, the experimental design and analysis
methods are almost identical, differing in the method
of causing poisoning agent and disease.
Galactosamine was administered orally to laboratory
rats of all groups, except the intact group, at a dose of
500 mg/kg for 4 days.
During the experiment, observation of the general
health and behavior of the rats, assessment of liver
function: taking blood samples and measuring the
levels of ALT, AST, bilirubin, histological analysis: taking
liver tissue, microscopic examination: microscopic
examination is carried out to identify changes in liver
cells (for example, inflammation, necrosis, fibrosis).
The obtained results were subjected to statistical
analysis and the influence of galactosamine on liver
poisoning was determined.
In any experiment, it is important to observe ethical
standards. It is necessary to obtain permission from the
ethics committee before using animals.
CONCLUSION
Each of the experimental models we studied is of
particular importance, and the preparations planned
for study should be studied in all four ways.
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