Disturbance of purine nucleotide metabolism - A possible early key event in development of intestinal damage induced by chemotherapy

Protective strategies to minimize the hematological toxicity in connection with bone marrow transplantation (BMT) have been successful, but toxicity t o the gastrointestinal tract prevents further dose escalation and therefore limits the application of the treatment. As it is known that chemotherapy leads to disruption of the intestinal barrier and morphological changes of mitochondria in enterocytes, this study was conducted in order to investiga te intestinal energy metabolism and permeability after intensive cytotoxic therapy in rats. Intestinal damage was produced by intraperitoneal administ ration of the cytostatic etoposide. Intestinal permeability was assessed by a [Cr-51]EDTA absorption test and intestinal purine nucleotide content by a high-performance liquid chromatography (HPLC) technique, Four hours after the administration of etoposide, and the next 48 hr, there was a significa nt increase in the intestinal permeability (P < 0.05) and a significant red uction of the purine nucleotide content in the intestinal epithelial cells (P < 0.01) as compared to control animals. This early disturbance in entero cyte energy metabolism may be a key event in the development of the intesti nal damage, induced by chemotherapy, and an explanation for the early disru ption of the intestinal barrier demonstrable before morphological changes a re evident.