The subject of the study was the hypothesis of the compromised intestinal barrier as a contributing cause for a high dose cyclophosphamide (CY) acute toxicity. The influence of high dose CY on the permeability of rat small intestine to luminal hydrophilic medium-sized molecules was estimated. The i/p administration of CY (600 mg/kg) resulted in the increased portal blood level of such molecules and increased flux of orally administered methylene blue into the portal system leading to the intense staining of the liver. Paracellular pathways of increased permeability of mucosa were predominant, judging by the increased [lactulose]/[mannitol] ratio in lactulose-mannitol urine excretion test. The probable enhancement of the translocation of toxic substances from the intestinal lumen into blood, contributing to CY toxicity, determines the clinical relevance of these data.
Key words
Cyclophosphamide; Rats; Gut barrier; Medium sized molecules; Methylene blue; Lactulose/mannitol test
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