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THE STUDY OF THE HEPATOPROTECTIVE EFFECT OF ANACARDIC ACID IN A
CARBON TETRACHLORIDE-INDUCED HEPATITIS MODEL
Akhmadova Maftuna
Master,
National University of Uzbekistan
Umarova Gulbakhor
Candidate of Biological Sciences,
Associate Professor of the
National University of Uzbekistan
Mukhamedova Mukambar
Lecturer at the Lyceum at TashPMI
Abstract.
This study explores the hepatoprotective effects of anacardic acid, a polyphenolic
compound, in a rat model of acute liver injury induced by carbon tetrachloride (CCl₄). Given the
increasing exposure to hepatotoxic xenobiotics from household, industrial, and agricultural
chemicals, the development of effective and multi-targeted hepatoprotective agents is critical. The
experiment was conducted in compliance with international animal ethics guidelines using Wistar
rats. The research assessed various doses of anacardic acid administered both orally and
intraperitoneally. Biochemical markers such as ALT, total protein, diene conjugates, and
malondialdehyde (MDA) levels were measured to evaluate liver function and oxidative stress.
The findings demonstrated that anacardic acid, particularly at a dose of 5 mg/kg administered
intraperitoneally, significantly mitigated liver damage, restored biochemical parameters, and
showed comparable efficacy to the standard hepatoprotective agent Karsil. These results suggest
that anacardic acid possesses promising hepatoprotective properties and warrants further
investigation as a potential therapeutic agent for hepatobiliary pathologies.
Keywords:
Anacardic acid, hepatotoxicity, carbon tetrachloride (CCl₄), hepatoprotection,
oxidative stress, liver enzymes, polyphenols, ALT, MDA, rats, acute liver injury.
Introduction.
Toxic liver damage is one of the most common etiological factors of hepatobiliary
pathology. It is associated with a significant increase in exposure to hepatotoxic xenobiotics,
including household, industrial, and agricultural chemicals. These exogenous factors not only
have specific mechanisms of action but also initiate a universal and potent endogenous
mechanism of hepatocyte damage in the form of oxidative stress [6]. The byproducts of this
process—aggressive and numerous reactive oxygen species (ROS)—lead to metabolic disorders,
membranopathies, functional impairments, mutations, accelerated apoptosis, and other forms of
cellular pathology.
Moreover, the multifactorial nature of toxic liver injury requires hepatoprotective agents to
provide multi-level protection, which is currently exhibited by only a limited number of
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hepatoprotectors (e.g., Legalon, Silybor, Hepaton) [5]. A characteristic feature of modern
hepatoprotective agents is their origin from plant-based raw materials and their content of
polyphenolic compounds with antioxidant activity, such as flavonoids, flavolignans, cinnamic
acids, and others [2].
Materials and Methods.
The study was conducted on 240 mature male and female Wistar rats
weighing between 170–280 grams, in accordance with the international recommendations of the
European Convention for the Protection of Vertebrate Animals Used for Experimental and Other
Scientific Purposes [1]. Acute liver injury was induced by administering a 50% solution of carbon
tetrachloride (CCl₄) orally using a metal atraumatic probe [7].
In the experiments, the polyphenol
anacardine
under investigation was administered using oral
and intraperitoneal routes. The polyphenol was given orally at doses of 100, 300, and 500 mg/kg
twice daily for 12 days via gastric intubation. Additionally, it was administered intraperitoneally
at doses of 5, 15, and 25 mg/kg twice daily for 12 days.
It should be noted that the tested polyphenol was administered for 5 days prior to the introduction
of carbon tetrachloride, and then concurrently with it for 7 days—specifically, 1 hour before each
administration of CCl₄ [3,7].
The acute toxicity of the studied drug was assessed in accordance with methodological guidelines
for evaluating the general toxic effects of pharmacological agents. The experiment was conducted
based on the method of V.V. Gatsura. After 14 days of administering the investigated preparation
to animals with carbon tetrachloride-induced liver damage, sodium etaminal was injected
intraperitoneally at a dose of 40 mg/kg. The duration of sleep (in lateral position) was recorded in
minutes. Statistical results were processed and expressed as the arithmetic mean (M) and its
standard error (m).
Sodium etaminal and the studied polyphenolic compound
anacardin
were administered orally in
different doses (100, 300, and 500 mg/kg), as well as intraperitoneally in doses of 5, 15, and 125
mg/kg. The assessment was performed under acute toxic liver injury conditions induced by
carbon tetrachloride, and sodium etaminal was administered intraperitoneally at a dose of 40
mg/kg on the 14th day of compound administration [6]. Control animals received the same
volume of purified water.
According to the obtained results, compared to the control group, administration of anacardin led
to a significant and reliable reduction in sleep duration — particularly by 55.7% at a dose of 100
mg/kg.
Results
. The observed reduction in sodium etaminal-induced sleep duration during administration
of the test compounds is likely due to the hepatoprotective effect, which preserves the activity of
the hepatic microsomal system responsible for catalyzing biotransformation reactions of
xenobiotics, mediated by endoplasmic reticulum enzymes of the cytochrome P450 system.
Our study focused on determining the optimal therapeutic dose of the investigated compound that
would normalize altered biochemical parameters in hepatocytes under conditions of carbon
tetrachloride-induced liver damage. To achieve this goal, the contribution of the compound was
evaluated based on its ability to normalize reduced total protein levels and elevated ALT enzyme
activity, both of which are typical markers observed during hepatocellular cytolysis.
In our experiments, we first determined the levels of diene conjugates. The concentration of diene
conjugates was expressed in µmol/L. Carbon tetrachloride (CCl₄) poisoning disrupted all liver
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functions: protein-synthetic activity (total protein content decreased by 27.2%), and severe
hepatocyte damage was observed through increases in serum diene conjugates and
malondialdehyde (MDA), a thiobarbituric acid-reactive substance (TBARS), by 41.2% and
175.1%, respectively, compared to the intact animal group.
When anacardine was administered orally at a dose of 100 mg/kg, levels of primary LPO products
(diene conjugates), final LPO products (TBARS, including MDA), and total protein in serum
remained significantly elevated compared to the intact control — 109.9%, 145.2%, and 88.5%,
respectively.
At a dose of 300 mg/kg, compared to 100 mg/kg, administration of anacardine resulted in a
significant reduction in serum diene conjugates and TBARS, with levels decreasing by 10.2% and
increasing by 20.6%, respectively, compared to control.
These results clearly show that CCl₄ intoxication disrupted all hepatic functions: protein synthesis
(with total protein decreasing by 26.2%), and caused severe hepatocellular damage, indicated by
increases in serum diene conjugates and MDA by 41.2% and 175.1%, respectively, compared to
the intact animal group.
General indicators, including survival rate, detailed biochemical analyses of blood serum and liver,
and data calculated based on the hepatoprotection coefficient, suggest that an intraperitoneal dose
of 5 mg/kg of anacardine may be recommended as an effective therapeutic dose.
Conclusion.
In carbon tetrachloride-induced hepatitis models, comparison of anacardine's
hepatoprotective effect with Karsil showed a reduction in serum diene conjugates (by 49%) and
TBARS levels in serum (by 36.4%) and liver (by 41.7%) compared to the control group.
Increased activity of ALT and decreased total protein levels, which are indicative of cytolysis,
were also normalized under the influence of the administered preparation.
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