ORIGINAL RESEARCH
Effect of cystamine on gastric propulsive function and gas exchange in the rat model of radiation-induced myeloablation
1 Golikov Research Clinical Center of Toxicology of the Federal Medical Biological Agency, Saint-Petersburg, Russia
2 State Scientific Research Test Institute of the Military Medicine of Defense Ministry of the Russian Federation, Saint-Petersburg, Russia
Correspondence should be addressed: Timur V. Schäfer
Lesoparkovaya, 4, Saint-Petersburg, 195043, Russia; ur.xednay@refahcs
Author contribution: Vakunenkova OA — experimental procedure; Ivnitsky JuJu — rationale, developing the experimental model, data interpretation and discussion; Danilova OA — tissue biochemistry studies; Schäfer TV — experimental procedure, data processing and visualization, developing the experimental model; Rejniuk VL — methodological guidance of gas exchange assessment. All authors contributed to discussion, manuscript writing and editing.
Compliance with the 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.
Radiation exposure of recipients before hematopoietic stem cell transplantation can cause gastrointestinal (GI) stasis. It is associated with complications of myeloablative radiation therapy: delayed vomiting, excess bacterial growth, endotoxicosis, systemic inflammation, and sepsis. The study was aimed to assess the possibility of GI stasis prevention by intragastric administration of cystamine dihydrochloride when using radiation-induced myeloablation. The severity of GI stasis, levels of enterocyte markers in the small intestinal tissues and the indicator of intestinal endotoxicosis, urinary indican excretion, were assessed in rats 72 h after the single total-body X-ray exposure to the dose of 9.64 Gy (1.1 LD99/30); the animals’ whole body oxygen consumption was recorded daily. Irradiation caused GI stasis with predominant gastric stasis, the 1.5–4.8-fold decrease in the cholinesterase and alkaline phosphatase activity in the small intestinal tissues, doubled the urinary indican excretion, the whole body oxygen consumption reduction by 17–32%. Cystamine administration generally prevented gastric stasis, but had no significant effect on the characteristics of radiation-induced enterocytopenia and did not prevent accumulation of chyme in the caecum, hyperindicanuria, radiation-induced spleen hypotrophy, and decrease in gas exchange rate. Cystamine is promising for testing in large animals as a selective agent for emergency prevention of gastric stasis during myeloablative radiation therapy.
Keywords: rats, gastrointestinal stasis, gastric stasis, indican, radiation myeloablation, cystamine, enterocytopenia, gas exchange