447
Volume 5, Issue 10: Special Issue
(EJAR)
ISSN: 2181-2020
MPHAPP
THE 6TH INTERNATIONAL SCIENTIFIC AND PRACTICAL
CONFERENCE
“
MODERN PHARMACEUTICS: ACTUAL
PROBLEMS AND PROSPECTS
”
TASHKENT, OCTOBER 17, 2025
in-academy.uz
EVALUATION OF THE STATE OF THE CARDIOVASCULAR SYSTEM OF
RABBITS UNDER INFLUENCE OF FREE AND BOUND FORM OF THE
CYTOSTATIC AGENT DOXORUBICIN
Usmonov Sh.T.
Tagayaliyeva N.A.
Baratov K.R.
Yakubova R.A.
Rakhmonova G.G.
Mukhitdinov B.I.
Kalanova M.A.
Turaev A.S.
Institute of Bioorganic Chemistry of the Academy of Sciences of the Republic of Uzbekistan,
Tashkent city, Republic of Uzbekistan
e-mail: usherzodbek.forwork@gmail.com
https://doi.org/10.5281/zenodo.17342190
Relevance:
Targeted drugs, which significantly reduce the toxic effects of cytostatic drugs, are
widely used in clinical practice for the treatment of cancer. The Institute of Bioorganic Chemistry of
the Academy of Sciences of the Republic of Uzbekistan has developed a polysaccharide-conjugated
form of doxorubicin (DOX), PGA-DOX, which has promising medical implications.
Purpose of the study:
to evaluate the functional state of the cardiovascular system of rabbits
when exposed to free and bound forms of DOX with the introduction of equivalent doses of the
cytostatic.
Materials and methods:
Rabbits weighing 2-2.5 kg (4 per group) were administered a single
intravenous injection of DOX at a dose of 2.0 mg/kg (Group 1), PGA-DOX at a dose of 23.5 mg/kg
(Group 2), and control animals (Group 3) were given water for injection in an equivalent volume.
Blood pressure (systolic, SBP, and diastolic, DBP) and heart rate (HR) were measured for 2 hours.
Results:
In the control group of animals, the blood pressure and heart rate indicators in the
experimental rabbits remained within the range of initial values throughout the observation period,
with some decrease in all three indicators 30 minutes after the intravenous injection. Similar dynamics
of the decrease in blood pressure and heart rate indicators 30 minutes after administration are
observed for both cytostatic drugs, however, with varying degrees of effect. 30 minutes after a single
intravenous administration of PGA-DOX to rabbits at a dose of 23.5 mg/kg, a statistically significant
decrease in SBP relative to the control is observed (up to 126.0±3.02 mmHg, p=0.0035), however,
the indicators are restored to the initial and control levels by the end of the observation (2 hours after
drug administration). DBP readings drop below control values within 10 minutes (p=0.026) of drug
administration and do not recover after 30 minutes (p=0.008) and 120 minutes (p=0.04) of
observation. Pulse rate also does not normalize—it remains below control values after 30 minutes
(p=0.037) and 120 minutes (p=0.008) of drug administration.
Administration of the free form of DOX at a dose of 2 mg/kg resulted in a more pronounced
suppression of the cardiovascular system function in rabbits. Thus, a significant decrease in SBP to
139.0±3.2 mmHg was observed already 10 min after intravenous administration of the drug
(p=0.045). By 30 min of observation, SBP dropped to 107.0±4.7 mmHg (p=0.0007) with some
recovery 2 hours after administration, but the indicator did not reach the control values (p=0.0024).
DBP was also significantly lower than the control throughout the entire observation period after
448
Volume 5, Issue 10: Special Issue
(EJAR)
ISSN: 2181-2020
MPHAPP
THE 6TH INTERNATIONAL SCIENTIFIC AND PRACTICAL
CONFERENCE
“
MODERN PHARMACEUTICS: ACTUAL
PROBLEMS AND PROSPECTS
”
TASHKENT, OCTOBER 17, 2025
in-academy.uz
administration (p<0.006). HR dropped significantly by 30 min of observation (p=0.04) and did not
recover by 120 min of the experiment (p=0.004).
When comparing the two forms of the drugs, it was found that the drug DOX (2 mg/kg) has a
greater inhibitory effect on the cardiovascular system: after 30 and 120 minutes of observation, the
SBP (p<0.008) and DBP (p<0.04) indicators were statistically significantly lower than with PG-DOX
(23.5 mg/kg).
Conclusions:
A single intravenous administration of DOX and PG-DOX to rabbits at a
therapeutic dose resulted in a toxic effect on cardiovascular function. A comparison of the two drugs
revealed a significantly greater inhibitory effect on the cardiovascular system for 2 hours after
administration for DOX (2.0 mg/kg) compared to PG-DOX (23.5 mg/kg) (p < 0.05).
