Hematological changes and structural morphological changes in the liver and spleen in mice against the background of acute toxic effects of cyclophosphan

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Abstract

Background. Disturbances in the body associated with bone marrow failure caused by the administration of lethal doses of cyclophosphan to animals make it possible to use this experimental model to solve important pathophysiological problems.

Aim. To reveal hematological changes and structural morphological changes in the liver and spleen in mice against the background of acute toxic effects of lethal doses of.cyclophosphan.

Material and methods. The studies were performed on 200 outbred male mice weighing 27–29 g. Acute cytotoxic syndrome was modeled by a single intraperitoneal injection of a solution of cyclophosphan at doses of 500 and 750 mg/kg of body weight. Blood sampling for hematological studies was carried out on the 3rd, 6th, 10th and 15th days of intoxication, and the removal of the liver and spleen for morphological studies was performed on the 6th and 15th days. Statistical analysis was performed using Statistica 10 and MS Excel. Results were presented as mean (M) ± standard error of the mean (mx). To determine the significance of differences between groups with a significance level of p <0.05, Fisher's test and Mann–Whitney U-test were used.

Results. Mortality against the background of acute cytotoxic action of cyclophosphan at doses of 500 and 750 mg/kg reached 83.3 and 100%. The initial content of leukocytes in the peripheral blood of mice was (8.6±2.3)×109/l, and on the 6th day of intoxication it decreased to (1.0±0.3)×109/l and (0.6±0.1)×109/l (p=0.01). Blast cells of all hematopoietic lineages were present in blood smears. In the morphological picture of the spleen, the connective tissue stroma was sharply distinguished, and the white and red pulps were almost completely absent. Signs of acute toxic effects of cyclophosphan were found in the liver tissue.

Conclusion. The course of acute cytotoxic syndrome caused by cyclophosphan is accompanied by high mortality, the development of pancytopenia, pronounced destructive changes in the spleen tissue and toxic changes in the liver tissue.

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About the authors

Georgiy Nikolaevich Kokaya

Aviastankoservice LLC; National Medical Research Center named after V.A. Almazov

Email: kkgeo@yandex.ru
ORCID iD: 0009-0003-6482-0171

Junior Researcher; Clinical Resident, Depart. of Fa­culty Therapy

Russian Federation, Moscow, Russia; St. Petersburg, Russia

Anna A. Kokaya

Aviastankoservice LLC

Author for correspondence.
Email: kann1812@yandex.ru
ORCID iD: 0009-0008-9659-5315

M.D., Cand. Sci. (Med.), Senior Researcher

Russian Federation, Moscow, Russia

Ekaterina Aleksandrovna Vasilieva

Privolzhsky Research Medical University; Institute of Biology and Biomedicine, National Research Nizhny Novgorod State University named after N.I. Lobachevsky

Email: VasilyevaKatya@yandex.ru
ORCID iD: 0000-0002-5559-282X

Cand. Sci. (Biol.), Assoc. Prof., Depart. of Normal Physiology named after N.Y. Belenkov; Research Associate, Central Research Laboratory; Department of Biochemistry and Biotechnology, Institute of Biology and Biomedicine

Russian Federation, Nizhny Novgorod, Russia; Nizhny Novgorod, Russia

Maria S. Guseva

Privolzhsky Research Medical University

Email: gusevamaria1@gmail.com
ORCID iD: 0000-0003-1493-8000

Junior Researcher, Depart. of Morphology, Central Research Laboratory

Russian Federation, Nizhny Novgorod, Russia

Irina V. Mukhina

Privolzhsky Research Medical University

Email: mukchinaiv@mail.ru
ORCID iD: 0000-0002-8811-0049

D. Sci. (Biol.), Head of Depart., Depart. of Normal Physiology named after N.Y. Belenkov

Russian Federation, Nizhny Novgorod, Russia

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Supplementary files

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2. Fig. 1. Daily lethality of mice during acute toxic effect of cyclophosphan; experiment 1 involved a single intraperitoneal injection of cyclophosphan at a dose of 500 mg/kg; experiment 2 involved a single intraperitoneal injection of cyclophosphan at a dose of 750 mg/kg; *statistically signi­ficant differences compared with the control group, p < 0.05 (Fisher’s criterion).

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3. Fig. 2. Morphological picture of the spleen exposed to the cytotoxic action of cyclophosphan: a, the spleen in the control group; b, the spleen exposed to the toxic action of cyclophosphan at doses of 500 and 750 mg/kg on day 6 of intoxication; c, the spleen exposed to the toxic action of cyclophosphan at doses of 500 and 750 mg/kg on day 15 of intoxication. Hematoxylin and eosin staining of all preparations. Magnification ×4.

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4. Fig. 3. Morphological picture of the liver exposed to the cytotoxic action of cyclophosphan: a, the liver in the control group; b, the liver exposed to the to­xic action of cyclophosphan at doses of 500 and 750 mg/kg on day 6 of intoxication; c, the liver exposed to the toxic action of cyclophosphan at doses of 500 and 750 mg/kg on day 15 of intoxication. Hematoxylin and eosin staining was used for all the preparations. Magnification ×20.

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