Modelling myeloablative cytostatic therapy with cyclophosphamide is accompanied by gastrointestinal stasis in rats

About authors

1 State Scientific Research Test Institute of the Military Medicine of Defense Ministry of the Russian Federation, Saint-Petersburg, Russia

2 Golikov Research Clinical Center of Toxicology of the Federal Medical Biological Agency, Saint-Petersburg, Russia

Correspondence should be addressed: Timur V. Schäfer
Lesoparkovaya, 4, Saint-Petersburg, 195043; ur.xednay@refahcs

About paper

Author contribution: Schäfer TV — developing the experimental model, study planning, experimental procedure, data processing and visualization; Ivnitsky JuJu — rationale, developing the experimental model, data interpretation; Rejniuk VL — setting up the experiment. All authors contributed to discussion, manuscript writing and editing.

Compliance with ethical standards: the study was carried out in accordance with the principles of bioethics, approved by the European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes (ETS N 123).

Received: 2021-12-14 Accepted: 2022-01-15 Published online: 2022-01-31
  1. Emadi A, Jones RJ, Brodsky RA. Cyclophosphamide and cancer: golden anniversary. Nature reviews. Clinical Oncology. 2009; 6 (11): 638–47.
  2. Brodsky RA. High dose cyclophosphamide treatment for autoimmune disorders. Scientific World Journal. 2002; 28 (2): 1808–15.
  3. Kharfan-Dabaja MA, Reljie T, El-Asmar J, Nishihori T, Ayala E, Hamadani M, et al. Reduced-intencity or myeloablative allogenic hematopoietic cell transplantation for mantle cell lymphoma: a systematic review. Future Oncology. 2016; 22 (12): 2631–42.
  4. Yee GC, McGuire TR. Allogeneic bone marrow transplantation in the treatment of hematologic diseases. Clinical Pharmacy. 1985; 4 (2): 149–60.
  5. Haioun C, Lepage E, Gisselbrecht C, Salles G, Coiffier B, Brice P, et al. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin’s lymphoma: final analysis d’Etude des lymphomes de l’Adulte study. Journal of Clinical Oncology. 2000; 18: 3025–30.
  6. Atilla E, Atilla PA, Demirer T. A review of myeloablative vs reduced intensity/non-myeloablative regimens in allogeneic hematopoietic stem cell transplantations. Balkan Medical Journal. 2017; 34 (1): 1–9.
  7. Legeza VI, Geleev ISh, Seleznyov AB. Emetic syndrome. Saint Petersburg: Foliant, 2005; 144 p. Russian.
  8. Ivnitsky JJ, Schäfer TV, Tyaptin AA, Rejniuk VL. Changes in the chemical composition of the blood and brain of rats under the conditions of modeling the myeloablation regimen of cyclophosphamide administration. Toxicologicheskiy vestnik. 2019; 156 (3): 13–8. Russian.
  9. Schäfer TV, Rejniuk VL, Ivnitsky JJ. Ammonia redistribution from the gastrointestinal tract to general circulation after intraperitoneal injection of cyclophosphamide to rats. Bulletin of Experimental Biology and Medicine. 2010; 150 (8): 170–6. Russian.
  10. Dore MP, Pes GM, Murino A, Quarta Colosso B, Pennazio M. Short article: small intestinal mucosal injury in patients taking chemotherapeutic agents for solid cancers. European Journal of Gastroenterology & Hepatology. 2017; 29 (5): 568–71.
  11. Schäfer TV, Ivnitsky JJ, Rejniuk VL. Cyclophosphamideinduced leakage of gastrointestinal ammonia into the common bloodstream in rats. Drug and Chemical Toxicology. 2011; 34 (1): 25–31.
  12. Ghareghani M, Reiter RJ, Zibara K, Fathadi N. Latitude, vitamin D, melatonin, and gut microbiota act in concert to initiate multiple sclerosis: a new mechanistic pathway. Frontiers in Immunology. 2018; 9: 2484.
  13. On Approval of the Rules of Good Laboratory Practice: Order of the Ministry of Health of the Russian Federation from April 1, 2016, No 199n. Мoscow, 2016.
  14. Guidelines for the maintenance and care of laboratory animals. Rules of equipment of premises and organization of procedures: GOST 33215–2014. Moscow: Standartinform, 2016; 12 p. Russian.
  15. Guidelines for the maintenance and care of laboratory animals. Rules for the maintenance and care of laboratory rodents and rabbits: GOST 33216–2014. Moscow: Standartinform, 2016; 15 p. Russian.
  16. Visnovský P. The effect of cyclophosphamide and methotrexate on gastric emptying and secretion in rats. Bratislavske lekarske listy. 1992; 93 (2): 90–2. Slovak.
  17. Anderson LW, Chen TL, Colvin OM, Grochow LB, Collins JM, Kennedy MJ, et al. Cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide kinetics in patients receiving high-dose cyclophosphamide chemotherapy. Clinical Cancer Research. 1996; 2 (9): 1481–7.
  18. De Jonge ME, Huitema AD, Rodenhuis S, Beijnen JH. Clinical pharmacokinetics of cyclophosphamide. Clinical Pharmacokinetics. 2005; 44 (11): 1135–64.
  19. Habriev RU, editor. Guidelines for the experimental (preclinical) study of new pharmacological substances. Moscow: Medicina, 2005; 832 p. Russian.
  20. Deane AM, Chapman MJ, Reintam Blaser A, McClave SA, Emmanuel A. Pathophysiology and treatment of gastrointestinal motility disorders in the acutely ill. Nutrition in Clinical Practice. 2019; 34 (1): 23–36.
  21. Frazer C, Hussey L, Bemker M. Gastrointestinal motility problems in critically ill patients. Critical care nursing clinics of North America. 2018; 30 (1): 109–21.
  22. Herbert MK, Holzer P. Standardized concept for the treatment of gastrointestinal dysmotility in critically ill patients–current status and future options. Clinical Nutrition. 2008; 27 (1): 25–41.
  23. Ukleja A. Altered GI motility in critically Ill patients: current understanding of pathophysiology, clinical impact, and diagnostic approach. Nutrition in Clinical Practice. 2010; 25 (1): 16–25.
  24. Buchholz BM, Bauer AJ. Membrane Tlr signaling mechanisms in the gastrointestinal tract during sepsis. Neurogastroenterology and Motility. 2010; 22: 232–45.
  25. Shimizu K, Ogura H, Asahara T, Nomoto K, Morotomi M, Nakahori Y, et al. Gastrointestinal dysmotility is associated with altered gut flora and septic mortality in patients with severe systemic inflammatory response syndrome: a preliminary study. Neurogastroenterology and Motility. 2011; 23 (4): 330–5.
  26. Chapman MJ, Nguyen NQ, Deane AM. Gastrointestinal dysmotility: clinical consequences and management of the critically ill patient. Gastroenterology clinics of North America. 2011; 40 (4): 725–39.
  27. Ivnitsky JJ, Schäfer TV, Rejniuk VL. Promotion of the toxic action of cyclophosphamide by digestive tract luminal ammonia in rats. ISRN Toxicology [Internet]. 2011. Article ID 450875. Available from: https://www.hindawi.com/journals/isrn/2011/450875/.