INTRAPERITONEAL ADMINISTRATION OF NUCLEOSIDE-NUCLEOTIDE MIXTURE INHIBITS ENDOTOXIN-INDUCED BACTERIAL TRANSLOCATION IN PROTEIN-DEFICIENT MICE

Nucleosides and nucleotides as a precursor for nucleic acid synthesis may be essential for rapidly growing cells, since intestinal epithelia l cells have limited capacity for the de novo purine and pyrimidine sy nthesis. The present study was undertaken to determine the effect of i ntraperitoneal administration of nucleoside-nucleotide mixture (NNM) o r saline on endotoxin-induced bacterial translocation, ileal histology , and cecal population levels in protein-deficient mice. Intraperitone al administration of NNM for 14 days was associated with reduced trans location of gram-negative enterics to the mesenteric lymph node and sp leen 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 th e intestinal wall in the saline treated group as compared to the NNM t reated group, suggestive of the efficacy of NNM in improving the gut a nd epithelial mucosal cells. However, the cecal population levels in b oth groups were not different. Additionally, the mice in the saline gr oup were more susceptible to the lethal effects of endotoxin as compar ed to the NNM group suggesting that NNM may be essential for the enhan cement of the host defense system. These results suggest that NNM may be used to an advantage to inhibit or reduce the incidence of endotoxi n-induced bacterial translocation and improved survival in protein-def icient mice.