toxreviewТоксикологический вестникToxicological Review0869-79223034-4611Federal Scientific Center of Hygiene named after F.F. Erisman10.36946/0869-7922-2019-3-13-18toxreview-194Research ArticleСтатьиИЗМЕНЕНИЯ ХИМИЧЕСКОГО СОСТАВА КРОВИ И ГОЛОВНОГО МОЗГА КРЫС ПРИ МОДЕЛИРОВАНИИ МИЕЛОАБЛЯЦИОННОГО РЕЖИМА ПРИМЕНЕНИЯ ЦИКЛОФОСФАНАCHANGES IN THE CHEMICAL COMPOSITION OF BLOOD AND BRAIN OF RATS UNDER THE CONDITIONS OF MODELING OF THE MYELOABLATION REGIMEN OF CYCLOPHOSPHAMIDE ADMINISTRATIONИвницкийЮ. Ю.IvnitskyYu. Yu.

Ивницкий Юрий Юрьевич, доктор медицинских наук, профессор, ведущий научный сотрудник

192019, г. Санкт-Петербург

Ivnitsky Jury Jurievich

195043, Saint Petersburg

neugierig@mail.ruШеферТ. В.SchaferT. V.

Шефер Тимур Васильевич, доктор медицинских наук, начальник отдела

195043, г. Санкт-Петербург

Schafer Timur Vasilievich

192019, Saint Petersburg

schafer@yandex.ruТяптинА. А.TyaptinA. A.

Тяптин Александр Андреевич, кандидат медицинских наук, научный сотрудник

195043, г. Санкт-Петербург

Tyaptin Alexander Andreevich

192019, Saint Petersburg

tyaptin@mail.ruРейнюкВ. Л.RejniukV. L.

Рейнюк Владимир Леонидович, доктор медицинских наук, заместитель директора по научной работе

192019, г. Санкт-Петербург

Rejniuk Vladimir Leonidovich

195043, Saint Petersburg

vladton@mail.ruФГБУН «Институт токсикологии» ФМБА РоссииРоссияInstitute of Toxicology, Federal Medical Biological AgencyRussian FederationФГБУ «Государственный научно-исследовательский испытательный институт военной медицины» Министерства обороны Российской ФедерацииРоссияState Scientific Research Test Institute of the Military Medicine, Ministry of Defense of the Russian FederationRussian Federation201928062019031318Copyright © Ивницкий Ю.Ю., Шефер Т.В., Тяптин А.А., Рейнюк В.Л., 20192019Ивницкий Ю.Ю., Шефер Т.В., Тяптин А.А., Рейнюк В.Л.Ivnitsky Y.Y., Schafer T.V., Tyaptin A.A., Rejniuk V.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.toxreview.ru/jour/article/view/194

При моделировании на крысах миелоабляционной цитостатической химиотерапии с применением циклофосфана наблюдалась фульминантная гипераммониемия, сопровождавшаяся увеличением содержания аммиака и глутамина, уменьшением содержания пировиноградной и молочной кислот в ткани головного мозга. Установлена положительная корреляция между показателями азотемии, с одной стороны, и содержанием в ткани мозга аммиака и глутамина, с другой. На фоне выполнения нагрузочной пробы с ацетатом аммония изменения химического состава крови и ткани головного мозга были более выраженными. Полученные данные свидетельствуют об интенсификации поступления в головной мозг из крови аммиака желудочнокишечного происхождения, что ведёт к истощению тканевого пула пирувата при введении циклофосфана в дозах, применяемых с целью миелоабляции. Такие изменения создают условия для нарушения энергетического обеспечения неврологических функций при проведении миелоабляционной цитостатической химиотерапии с использованием циклофосфана.

When modeling myeloablation cytostatic chemotherapy with cyclophosphamide in rats fulminant hyperammonemia was observed accompanied by an increase in the content of ammonia and glutamine, a decrease in the content of pyruvic and lactic acids in brain tissue. A positive correlation between the indicators of azotemia and the content of ammonia and glutamine in brain tissue was established. In loading test with ammonium acetate changes in the chemical composition of blood and brain tissue were more pronounced. The data obtained indicate the intensification of the intake of gastrointestinal ammonia into the brain from the blood, which leads to the depletion of the tissue pool of pyruvate with the introduction of cyclophosphane in doses used for myeloablation. Such changes create the conditions for disruption of energy supply of neurological functions during myeloablative cytotoxic chemotherapy using cyclophosphamide.

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The authors declare that there are no conflicts of interest present.