OFFICIAL JOURNAL OF THE SCIENTIFIC SOCIETY OF
ANATOMISTS, HISTOLOGISTS, EMBRYOLOGISTS AND
TOPOGRAPHIC ANATOMISTS OF UKRAINE
ВІСНИК МОРФОЛОГІЇ
REPORTS OF MORPHOLOGY
DOI: 10.31393
ISSN 1818-1295
eISSN 2616-6194
Vol. 27, №1, 2021
Scientific peer-reviewed journal in the fields of normal and pathological anatomy, histology, cytology
and embryology, topographical anatomy and operative surgery, biomedical anthropology, ecology,
molecular biology, biology of development
Published since 1993
Periodicity: 4 times a year
Vinnytsya 2021
ORIGINAL ARTICLES
ВIСНИК МОРФОЛОГIЇ - REPORTS OF MORPHOLOGY
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Anatomists of Ukraine" and National Pyrogov Memorial Medical University, Vinnytsya in 1993
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Professional scientific publication of Ukraine in the field of medical sciences in specialties 221, 222, 228, 229
According to the list of professional scientific publications of Ukraine, approved by the order of the Ministry of Education and Science of Ukraine
No. 1188 of 24.09.2020
Professional scientific publication of Ukraine in the field of biological sciences in specialty 091
According to the list of professional scientific publications of Ukraine, approved by the order of the Ministry of Education and Science of Ukraine
No. 1471 of 26.11.2020
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ORIGINAL ARTICLES
CONTENT
Kostiuk O.H., Hodovan N.L., Gormash P.P., Taran I.V., Grebeniuk D.I., Mashevska O.V. Morphological
changes in the heart of rats after serial intravesical administration of Doxorubicin ............................................ 5
Vilkhova I.V. Biochemical parameters of blood and urine of rats at six-week administration of Nalbuphine .... 12
Pshychenko V.V., Cherno V.S.Morphometric features of rat pinealocytes in conditions of chronic
ethanol intoxication ..................................................................................................................................... 17
Vergeles T.M. Features of educational adaptation of young girls and young boys who are in institutions
of higher medical education, using the distance format of the educational process ........................................ 23
Kuzmenko Y.Y., Shevchenko О.О., Nazar P.S., Haidai O.S. Macro-microscopic changes in the
kidneys of the rats affected by methyl tertiary butyl ether in different time of the research .............................. 32
Mostovoy Y.M., Danilevych T.D. Sex-age features of the prevalence and structure of heart rhythm
disorders in the patients with severe Covid-infection...................................................................................... 41
Gasparyan K.A., Kondratyuk V.K., Ponomareva I.G., Kondratyuk K.O., Dzis N.P., Lisyana T.O.
Features of vaginal microbiocenosis in women of reproductive age with overweight and obesity ...................... 50
Petrushenko V.V., Grebeniuk D.I., Liakhovchenko N.A., Gormash P.P. Gallbladder cholesterolosis
in patients with metabolic syndrome and chronic pancreatitis ....................................................................... 58
Fedosieieva O.V., Pototska O.I. Immunohistochemical features of expression and distribution of
antibodies to thyroglobulin in the thyroid glands of newborn rats after prenatal exposure of dexamethasone ... 66
Shevchuk T.Ya., Pshybelskyj V.V., Zhuravlov O.A., Zhuravlova O.V. Indicators of cardiovascular
system in persons of mature age depending on a body constitution under adverse ecological conditions ....... 72
REPORTS OF MORPHOLOGY
Official Journal of the Scientific Society of Anatomists,
Histologists, Embryologists and Topographic Anatomists
of Ukraine
Morphological changes in the heart of rats after serial intravesical
administration of Doxorubicin
Kostiuk O.H.
1
, Hodovan N.L.
1
, Gormash P.P.
2
, Taran I.V.
1
, Grebeniuk D.I.
1
, Mashevska O.V.
1
1
National Pirogov Memorial Medical University, Vinnytsya, Ukraine
2
Utility non-profit enterprise "Vinnitsa Regional Pathological Bureau of Vinnitsa Regional Council", Vinnytsya, Ukraine
Along with a pronounced antitumor effect, Doxorubicin causes systemic effects with
damage to vital organs, including the heart. It prompts the search for ways to prevent the
cardiotoxic effect of the drug, one of which could be its intravesical administration. The
aim of the study was to develop a method of serial intravesical administration of
Doxorubicin in medium therapeutic doses in an experiment and to evaluate the
cardiotoxic effect of the drug. 42 female Wistar rats were included in the study. The
control group consisted of 7 intact rats. The experimental group consisted of 35 rats
who received intravesical chemotherapy with Doxorubicin at a dose of 5 mg/kg once a
week for 5 weeks. On days 7th, 14th, 21st, 28th, 35th the hearts of experimental animals
were taken for morphological examination. Histomorphometrically determined: the
diameter of cardiomyocytes (in the middle part) and the transverse diameter of their
nucleus, the width of the interstitial space (endo- and perimysium). The data of
histomorphological and histomorphometric examination of the myocardium testified
that all animals of the experimental group had a circulatory disorder in the heart muscle
at the level of hemomicrocirculation. Such changes led to cardiomyocyte hypotrophy,
interstitial edema and fibrosis. During intravesical chemotherapy, the animals showed
marked changes in the myocardium, such as expansion of the endomysial zone, due to
capillary congestion and edema, in comparison with animals of the intact group. At the
end of the experiment, the animals of the experimental group retained the expansion of
the endomysial zone, mainly due to interstitial fibrosis. Such changes indicate myocardial
hypoxemia with damage and death of cardiomyocytes, activation of interstitial and
replacement collagen formation. The obtained morphological data partially indicate
the development of dilated cardiomyopathy in experimental animals. However, these
changes were less pronounced than the previously described changes that occur after
systemic administration of the drug. Additional studies of the electrophysiological
activity of the heart and biochemical markers will make it possible to fully assess the
degree of cardiotoxicity of Doxorubicin after its intravesical administration. Thus,
serial intravesical administration of Doxorubicin in moderate therapeutic doses
according to the proposed method causes changes in the myocardium of experimental
animals, which are partially similar to the changes in the heart of people receiving
chemotherapy with this drug.
Keywords: Doxorubicin, cardiomyopathy, morphology, experiment, rats, intravesical.
ARTICLE INFO
Received: 16 November 2020
Accepted: 6 January 2021
UDC: 616-006:615.277.3 + 591.412 +
59.089
CORRESPONDING AUTHOR
e-mail: scienceandroid@gmail.com
Taran I.V.
© 2021 National Pirogov Memorial Medical University, Vinnytsya
DOI: 10.31393/morphology-journal-2021-27(1)-01 Reports of Morphology, Vol. 27, №1, Pages 5-11
ISSN 1818-1295 eISSN 2616-6194
journal homepage: https://morphology-journal.com
5
Introduction
Due to the tendency to a constant increase in overall
morbidity and mortality, bladder cancer remains an urgent
problem of modern medicine in general and oncology in
particular [10, 16].
Bladder canc er ranks fourth in the structure of
oncopathology in the United States and Europe. In terms
of mortality, this pathology ranks seventh and eighth in the
structure of mortality from tumor diseases in the United
States [18] and Europe, respectively [4]. Men suffer from
bladder cancer about 3-4 times more often than women.
According to statistics, every 26th man will develop bladder
cancer during his lifetime [18]. At the same time, the overall
five-year survival rate in Europe is about 68% [2].
Due to the constant improvement of diagnostic
6
ISSN 1818-1295 eISSN 2616-6194 Reports of Morphology
Morphological changes in the heart of rats after serial intravesical administration of Doxorubicin
algorithms, more and more newly diagnosed cases (up to
75% according to some data) are superficial bladder
cancer, when the tumor affects only the mucous membrane
or submucosal layer [1].
Transurethral resection of the tumor is a common
standard in the treatment of patients with superficial bladder
cancer [12, 22]. Intravesical chemotherapy and/or
immunotherapy are used as adjuvant therapy after
transurethral resection to prevent the development of
residual and recurrent neoplasms [17, 25].
The intravesical route of drug administration opens wide
opportunities for scientists and practitioners to develop new
and optimize existing treatments for non-invasive bladder
cancer [17, 25]. One such optimization method is
intravesical administration of Doxorubicin, which has
proven itself in systemic administration [5], although it has
led to the development of Doxorubicin-induced
cardiomyopathy [7, 9, 15, 21].
Given the morphological features of the structure of the
mucous membrane of the bladder, the absorption of the
chemotherapy into the systemic bloodstream, and
accordingly its systemic effects should be minimal [8, 20].
However, this problem requires large-scale studies,
including a preclinical study of the cardiotoxicity of
Doxorubicin by intravesical administration.
The aim of the study was to develop a method of serial
intravesical administration of Doxorubicin in moderate
therapeutic doses in the experiment and to evaluate the
cardiotoxic effect of the drug.
Materials and methods
The experimental study was performed on the basis of a
research laboratory of preclinical study of pharmacological
substances of National Pirogov Memorial Medical University,
Vinnytsya.
All experiments were performed in accordance with the
"Regulations on the use of animals in biomedical
experiments" with the permission of the Bioethics Committee
and in accordance with the provisions of Directive 2010/63/
EU of the European Parliament and of the Council of 22
September 2010 "On the protection of animals used for
scientific purposes".
The study included 42 female Wistar rats under 1 year of
age and weighing 120.0 to 220.0 grams (192.0±15.2 grams).
The control group consisted of 7 intact rats, which were
selected to determine the main studied morphological and
morphometric parameters in the norm. The experimental
group consisted of 35 rats who underwent intravesical
chemotherapy with Doxorubicin according to the author's
method (Patent of Ukraine for utility model 138090 from
25.11.2019).
The technique consisted of intravesical administration
of Doxorubicin at a dose of 5 mg/kg once a week for 5 weeks.
The dose of 5 mg/kg was determined by recalculating the
average therapeutic dose of the drug for humans in the
treatment of superficial bladder cancer. The recalculation
was performed according to the method proposed by A.B.
Nair and Sh. Jacob (2016) [13].
Direct administration of the drug into the bladder was
performed according to the author's method - a method of
serial intravesical administration of drugs in female rats
(Patent of Ukraine for utility model 138092 from
25.11.2019) using a special catheter (Patent of Ukraine for
utility model 139761 from 27.01.2020). The catheter is a
flexible tube with a diameter of 2 Fr (0.67 mm) and a length
of 20 mm, at one end of which is an oil with a diameter of 6
Fr (2.0 mm), which does not cover the lumen of the catheter.
The catheter was inserted into the bladder and drugs were
administered as follows. Under general anesthesia, a lower-
middle laparotomy was performed in experimental rats. The
body of the bladder was removed into the surgical wound. A
longitudinal cystotomy 3 mm long was performed.
Antegradely conducted the tubular part of the catheter through
the inner opening of the urethra through the urethra to the
outside. The bladder was sutured. Performed revision of
the abdominal cavity and washing it with an antiseptic
solution. The laparotomy wound was sutured tightly in layers.
To prevent the cytostatic effect of Doxorubicin on the wound
surface, its administration was started one week after
catheter placement, when there was a complete restoration
of the integrity of the bladder wall. To administer Doxorubicin,
the tubular part of the catheter located in the outer opening of
the urethra was fixed with tweezers. The syringe needle was
inserted into the catheter hole and the drug was injected
into the bladder.
One week after each administration of the drug (7, 14,
21, 28, 35 days), 7 rats were randomly selected and removed
from the experiment by dislocation of the cervical vertebrae
under ketamine anesthesia at the rate of 0.22 ml per 100
grams of weight of the experimental animal.
After dissection, the heart was removed, followed by
fixation in 10% neutral formalin solution. After fixation for 3
days, cardiac samples were prepared according to standard
methods. Paraffin sections 5-7 μm thick were stained with
hematoxylin and eosin. Microscopy and photographing of
histological specimens were performed using a light
microscope OLIMPUS BX 41 at magnifications of 40, 100,
200, 400 and 1000. Microscopy assessed the condition of
the myocardium, the presence and nature of pathological
and compensatory-adaptive changes in it.
Image acquisition and processing, as well as
morphometry were performed using the program "Quick
PHOTO MICRO 2.3". Histomorphometrically determined: the
diameter of cardiomyocytes (in their middle part) and the
transverse diameter of their nucleus, the width of the interstitial
space (endo- and perimysia).
The obtained data were processed using the statistical
software package SPSS 20.0 for Windows.
Results
The results of microscopic examination of the
myocardium of the control group of animals are described