449
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
ANALYSIS OF GENE EXPRESSION PROFILE CHANGES FOLLOWING THERAPY
WITH 4-[(3-ETHOXY-3-OXOPROPANOYL) AMINO] BENZOIC ACID IN
EXPERIMENTAL CHRONIC HEART FAILURE
Grishina A.Yu.
Federal State Budgetary Educational Institution of Higher Education "Saint Petersburg State
Chemical Pharmaceutical University", St. Petersburg city, Russian Federation
e-mail: grishina.anna@pharminnotech.com
https://doi.org/10.5281/zenodo.17342222
Topicality. Chronic heart failure (CHF) is associated with systemic oxidative stress and
significant impairment of cellular metabolism, contributing to damage to target organs, particularly
the kidneys. Current therapeutic approaches have limited efficacy in correcting these metabolic
disorders. Succinate dehydrogenase (SDH) inhibitors, such as 4-[(3-ethoxy-3-oxopropanoyl) amino]
benzoic acid (etmaben), are considered potential agents for metabolic therapy; however, their
molecular mechanisms of action in established CHF remain poorly understood.
Aim.
To evaluate the effect of 4-[(3-ethoxy-3-oxopropanoyl) amino] benzoic acid on the
expression of key genes regulating antioxidant defense, energy metabolism, and cellular homeostasis
in the kidney tissue of rats with experimental chronic heart failure.
Materials and Methods
: The study was conducted on 30 outbred male rats divided into groups:
intact control, rats with a CHF model induced by left coronary artery ligation, and CHF rats treated
with etmaben from day 30 to day 61 after surgery. The mRNA levels of the genes Nrf2, Gpx1, Cpt1b,
Hes1, mTOR, Nox1, and Txnrd1 were assessed in kidney homogenates using real-time polymerase
chain reaction (RT-qPCR). Statistical significance of differences was determined using Student's t-
test or one-way analysis of variance (ANOVA) followed by Tukey's post-hoc test.
Results
. CHF was found to lead to a significant activation of the transcription factor Nrf2;
however, the expression of its target gene, GPx1, was unchanged in both CHF and etmaben-treated
groups, indicating dysfunction of this pathway. Therapy with 4-[(3-ethoxy-3-oxopropanoyl) amino]
benzoic acid caused a statistically significant increase in the expression of the Cpt1b gene (p < 0.05),
suggesting a shift in cellular metabolism towards fatty acid β-oxidation. A significant suppression of
the pro-oxidant enzyme Nox1 and activation of the thioredoxin reductase 1 (Txnrd1) gene (p < 0.05)
were also revealed in the treatment groups. The Notch signaling pathway was activated under the
influence of etmaben, as evidenced by increased Hes1 gene expression (p < 0.05), while no
statistically significant effect on mTOR gene expression was observed.
Conclusions.
Administration of etmaben against the background of established CHF does not
restore the function of the Nrf2/GPx1 pathway, which may be associated with the blockade of target
gene transcription induced by succinate accumulation. The mechanism of action of 4-[(3-ethoxy-3-
oxopropanoyl) amino] benzoic acid under conditions of experimental CHF can be characterized as
metabolic modulation promoting cellular stabilization under chronic stress.
