Влияние внутрижелудочного введения гидрокарбоната натрия или соляной кислоты на кишечную эндотоксемию у крыс при миелоабляции циклофосфамидом

Abstract

Toxic effects of the myeloablative cyclophosphamide (CP) doses include damage to the gastrointestinal tract. This is manifested by gastrointestinal stasis, cytostatic drug-induced damage to the small intestinal mucosa, and acute gut-derived endotoxemia. The study was aimed to identify causal relationships between gastrointestinal stasis, enterocytopenia, and acute gut-derived endotoxemia in the rat model of the CP myeloablative conditioning. We assessed the effects of the intragastrically administered 0.48 М sodium bicarbonate (NaHCO3) solution or the 0.1 М hydrochloric acid (HCl) solution on the indicators of gastrointestinal stasis, enterocytopenia, portal blood levels of endotoxin, ammonia, urea, and urinary indican excretion. The stomach overfilled with chyme, decreased alkaline phosphatase and cholinesterase activity in the small intestinal tissues, 4.4-fold increased endotoxin levels, 4.6-fold increased urea levels, twofold increased portal blood plasma creatinine levels, and twofold increased urinary indican excretion were observed three days after intravenous administration of CP in a dose of 390 mg/kg. Intragastric administration of NaHCO3 or HCl partially prevented gastric stasis, but not acute gut-derived endotoxemia. Administration of NaHCO3, not HCl, prevented enterocytopenia in the duodenum. Acute gut-derived endotoxemia resulted mainly from the more intense release of the cecal microflora waste products into blood. Testing the use of sodium bicarbonate intragastric administration combined with the enteral detoxification and/or options for suppression of colonic microflora vegetation for prevention of the myeloablative cytostatic therapy complications is promising.