Влияние гидрокарбоната натрия на формирование гастростаза у крыс при моделировании миелоабляционной химиотерапии циклофосфаном

Abstract

Myeloablative cytostatic therapy is often associated with gastrointestinal (GI) stasis that is a component of pathogenesis of the bacterial overgrowth syndrome, endotoxicosis, systemic inflammation, sepsis, emetic syndrome. The study was aimed to test the hypothesis that sodium bicarbonate (NaHCO3), the alkalinizing agent administrated by gavage in the rat model of myeloablative cytostatic therapy with cyclophosphamide (CP), would have a protective effect against GI stasis. We assessed the effects of intragastric NaHCO3 administrations on the development of GI stasis, acute chemotherapy-induced mucositis of the small intestine, and urinary excretion of indican using 140 Wistar rats with the body weight of 161–190 g as a model of myeloablative cytostatic therapy with the intravenously injected CP. The CP administration in a dose of 390 mg/kg resulted in dystrophic changes in the small intestinal mucosa, the development of GI stasis with predominant gastric stasis within the first 24 h, and the increase in excretion of indican. Intragastric administration of NaHCO3 in a dose equivalent to 350 mL of the 4% NaHCO3 solution in humans to rats 30 min before and immediately after the CP administration prevented acute chemotherapy-induced mucositis of the small intestine and alleviated the symptoms of gastric stasis and excessive growth of the indole-producing gastrointestinal microbiota. The reported approach to emergency drug prevention of the myeloablative cytostatic drug therapy gastrointestinal complications holds promise for testing of the use of CP and other alkylating drugs as cytostatic agents.