Hematological changes and structural morphological changes in the liver and spleen in mice against the background of acute toxic effects of cyclophosphan
Georgiy Nikolaevich Kokaya , Anna A. Kokaya , Ekaterina Aleksandrovna Vasilieva , Maria S. Guseva , Irina V. Mukhina
Kazan medical journal ›› 2023, Vol. 104 ›› Issue (4) : 523 -533.
Hematological changes and structural morphological changes in the liver and spleen in mice against the background of acute toxic effects of cyclophosphan
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.
cytotoxicity / cyclophosphan / pancytopenia / hematological parameters / morphological changes / experimental modeling
| [1] |
Vladimirskaya EB. Normal hematopoiesis and its regulation. Clinical oncohematology. Basic research and clinical practice. 2015;8(2):109–119. (In Russ.) |
| [2] |
Владимирская Е.Б. Нормальное кроветворение и его регуляция. Клиническая онкогематология. Фундаментальные исследования и клиническая практика. 2015;8(2):109–119. EDN: TYMYAP. |
| [3] |
Gematologiya. Rukovodstvo dlya vrachey. (Hematology. A guideline for doctors.) NN Mamaeva, editor. 3d ed. St. Petersburg: SpeczLit; 2019. 639 p. (In Russ.) |
| [4] |
Гематология. Руководство для врачей. Под ред. Н.Н. Мамаева. Изд. 3-е, испр. и доп. СПб.: СпецЛит; 2019. 639 с. |
| [5] |
Goldberg ED, Dygay AM, Zhdanov VV. The role of cytokines in dinamic theory of hemopoiesis. Medical immunology. 2001;3(4):487–497. (In Russ.) |
| [6] |
Гольдберг Е.Д., Дыгай А.М., Жданов В.В. Динамическая теория регуляции кроветворения и роль цитокинов в регуляции гемопоэза. Медицинская иммунология. 2001;3(4):487–497. EDN: JUASED. |
| [7] |
Goldberg ED, Dygai AM, Zhdanov VV. The mechanisms of blood system regulation under myelosuppressive influences. Byulleten sibirskoy meditsiny. 2002;1(2):7–16. (In Russ.) |
| [8] |
Гольдберг Е.Д., Дыгай А.М., Жданов В.В. Механизмы регуляции системы крови при миелосупрессирующих воздействиях. Бюллетень сибирской медицины. 2002;1(2):7–16. EDN: UPSQFF. |
| [9] |
Rukovodstvo po gematologii. (A guideline of Hematology.) AI Vorob’ev, editor. 3d ed. M.: N`yudiamed; 2005. 450 p. (In Russ.) |
| [10] |
Руководство по гематологии. Под ред. А.И. Воробьёва. Изд. 3-е, испр. и доп. М.: Ньюдиамед; 2005. 450 с. |
| [11] |
Transfuziologiya. Natsional`noe rukovodstvo. (Transfusiology. National guidelines.) АА Ragimov, editor. Moscow: GEOTAR-Media; 2012. 1184 p. (In Russ.) |
| [12] |
Трансфузиология. Национальное руководство. Под ред. А.А. Рагимова. М.: ГЭОТАР-Медиа; 2012. 1184 с. |
| [13] |
Klinicheskaya onkogematologiya. Rukovodstvo dlya vrachey. (Clinical Oncohematology. A guideline for doctors.) MA Volkova, editor. M.: Medicina; 2001. 576 p. (In Russ.) |
| [14] |
Клиническая онкогематология. Руководство для врачей. Под ред. М.А. Волковой. М.: Медицина; 2001. 576 с. |
| [15] |
Kutsenko SA, Butomo NV, Grebenyuk AN. Voennaya toksikologiya, radiobiologiya i meditsinskaya zashhita. (Military Toxicology, Radiobiology and Medical Defense.) St. Petersburg: Foliant; 2004. 528 p. (In Russ.) |
| [16] |
Куценко С.А., Бутомо Н.В., Гребенюк А.Н. Военная токсикология, радиобиология и медицинская защита. СПб.: Фолиант; 2004. 528 с. |
| [17] |
Nikiforov AS, Ivanov IM, Sventickaya AM. Modeling of acute radiation bone marrow syndrome in the experiment on mice. Medical-biological and social-psychological issues of safety in emergency situations. 2017;(4):66–73. (In Russ.) DOI: 10.25016/2541-7487-2017-0-4-66-73. |
| [18] |
Никифоров А.С., Иванов И.М., Свентицкая А.М. Моделирование острого лучевого костномозгового синдрома в эксперименте на мышах. Медико-биологические и социально-психологические проблемы безопасности в чрезвычайных ситуациях. 2017;(4):66–73. DOI: 10.25016/2541-7487-2017-0-4-66-73. |
| [19] |
Kokaya GN, Kokaya AA, Kozyakov VP, Zavirsky AV, Zacepin VV, Basharin VA, Tsygan VN, Mavrenkov EM. Experimental evaluation of the radiomodifying efficiency of low-intensity electromagnetic radiation in acute X-ray irradiation of mice. Bulletin of the Russian Military Medical Academy. 2021;23(2):131–138 (In Russ.) DOI: 10.17816/brmma.65944. |
| [20] |
Кокая Г.Н., Кокая А.А., Козяков В.П., Завирский А.В., Зацепин В.В., Башарин В.А., Цыган В.Н., Мавренков Э.М. Экспериментальная оценка радиомодифицирующей эффективности низкоинтенсивного электромагнитного излучения при остром рентгеновском облучении мышей. Вестник Российской военно-медицинской академии. 2021;23(2):131–138. DOI: 10.17816/brmma.65944. |
| [21] |
Ivnitskiy YuYu, Shefer TV, Tyaptin AA, Rejnyuk VL. Changes in the chemical composition of blood and brain of rats under the conditions of modeling of the myeloablation regimen of cyclophosphamide administration. Toxicological review. 2019;156(3):14–18. (In Russ.) DOI: 10.36946/0869-7922-2019-3-13-18. |
| [22] |
Ивницкий Ю.Ю., Шефер Т.В., Тяптин А.А., Рейнюк В.Л. Изменения химического состава крови и головного мозга крыс при моделировании миелоабляционного режима применения циклофосфана. Токсикологический вестник. 2019;156(3):14–18. DOI: 10.36946/0869-7922-2019-3-13-18. |
| [23] |
Dygai AM, Zhdanov VV. The theory of hemopoiesis regulation in health and disease. Byulleten SO RAMN. 2012;32(1):21–30. (In Russ.) |
| [24] |
Дыгай А.М., Жданов В.В. Теория регуляции кроветворения в норме и при патологии. Бюллетень СО РАМН. 2012;32(1):21–30. EDN: OPUFHX. |
| [25] |
Kukes VG, Sy`cheva DA. Klinicheskaya farmakologiya. Uchebnik. (Clinical Pharmacology. Textbook.) 6th ed. M.: GEOTAR-Media; 2021. 1024 p. (In Russ.) |
| [26] |
Кукес В.Г., Сычева Д.А. Клиническая фармакология. Учебник. Изд. 6-е, испр. и доп. М.: ГЭОТАР-Медиа; 2021. 1024 с. |
| [27] |
Karkishсhenko NN. Osnovy` biomodelirovaniya. (Fundamentals of Biomodeling.) M.: Mezhakademicheskoe izdatel`stvo VPK; 2004. 608 p. (In Russ.) |
| [28] |
Каркищенко Н.Н. Основы биомоделирования. М.: Межакадемическое издательство ВПК; 2004. 608 c. |
| [29] |
Bhat N, Kalthur SG, Padmashali S, Monappa V. Toxic effects of different doses of Cyclophosphamide on liver and kidney tissue in swiss albino mice: A histopathological study. Ethiop J Health Sci. 2018;28(6):711–716. DOI: 10.4314/ejhs.v28i6.5. |
Eco-Vector
/
| 〈 |
|
〉 |