Riboflavin deficiency: early effects on post-weaning development of the duodenum in rats

The aim of this present study was to identify the earliest point at which r iboflavin deficiency affects post-weaning bowel development in rats. After weaning, eighty Wistar rats were weight-matched as pairs, one animal being fed a normal synthetic diet and the other being fed the same diet but defic ient in riboflavin. Body weight, feeding and rates of growth were monitored and eight pairs of animals were taken for analysis at 45, 69, 93, 117 and 141 h. Riboflavin status was monitored by determining the erythrocyte gluta thione reductase activation coefficient (EGRAC), and hepatic flavins were m easured by a fluorescence assay. Changes to the number and dimensions of vi lli and crypts in the duodenum were determined, as well as crypt division ( bifurcation) and the DNA synthesis index of the crypt epithelium by bromode oxyuridine (BrdU) labelling. Riboflavin deficiency was established in the e xperimental rats, as demonstrated by a significant increase in EGRAC after 45 h (P <0.001) and decreased liver flavins after 96 h (P <0.001). After 96 h a significant increase in the size and cellularity of the crypts (P <0.0 01 in both cases) was seen in these riboflavin-deficient animals, with a de creased incidence of bifurcating crypts and of BrdU-labelled cells. No chan ges to villus number or size were observed. The present study has demonstra ted that developmental changes to the duodenal crypt arise shortly after ci rculating riboflavin measurements show evidence of deficiency. These change s primarily affect cell proliferation and crypt bifurcation, and precede lo ng-term changes such as the reduction of villus number.