Intraperitoneal administration of nucleoside-nucleotide mixture inhibits endotoxin-induced bacterial translocation in protein-deficient mice.

Abstract

Nucleosides and nucleotides as a precursor for nucleic acid synthesis may be essential for rapidly growing cells, since intestinal epithelial cells have limited capacity for the de novo purine and pyrimidine synthesis. The present study was undertaken to determine the effect of intraperitoneal administration of nucleoside-nucleotide mixture (NNM) or saline on endotoxin-induced bacterial translocation, ileal histology, and cecal population levels in protein-deficient mice. Intraperitoneal administration of NNM for 14 days was associated with reduced translocation of gram-negative enterics to the mesenteric lymph node and spleen in comparison to saline. Histologically, the extent of the damage to the gut mucosa was greater in the saline group. This was confirmed by the profound diminution of the villous height, crypt depth, and the intestinal wall in the saline treated group as compared to the NNM treated group, suggestive of the efficacy of NNM in improving the gut and epithelial mucosal cells. However, the cecal population levels in both groups were not different. Additionally, the mice in the saline group were more susceptible to the lethal effects of endotoxin as compared to the NNM group suggesting that NNM may be essential for the enhancement of the host defense system. These results suggest that NNM may be used to an advantage to inhibit or reduce the incidence of endotoxin-induced bacterial translocation and improved survival in protein-deficient mice.