VITAMIN-A-DEFICIENCY EXACERBATES METHOTREXATE-INDUCED JEJUNAL INJURY IN RATS

Two studies were conducted to investigate whether vitamin A-deficient rats were more susceptible to intestinal injury caused by methotrexate (MTX), since vitamin A deficiency alone causes only mild changes to j ejunal structure and function. Weanling male rats were fed a vitamin A -deficient diet (-VA) for 40-42 d and compared to rats either pair-fed (PF) or with free access (+VA) to the same diet. Drinking water of PF and +VA rats was supplemented with 37.5 mu g (Study 1) or 75 mu g (St udy 2) vitamin A (Rovimix A 500W)/d. Rats in each group received MTX ( -VAMTX, PFMTX, +VAMTX) or vehicle. MTX administration reduced intestin al mucosal wet weight, protein and DNA concentrations, and sucrase and maltase activities in -VA and PF rats (P < 0.02). In Study 1, -VAMTX rats developed a severe jejunal enteropathy and had a higher incidence of diarrhea (P < 0.005), greater weight loss (P < 0.005), more disrup tion of villus architecture (P < 0.0001) and lower disaccharidase acti vity (P < 0.007) than PFMTX rats. Similar results were observed in Stu dy 2. Liver retinol concentration (but no other variable) was greater in rats receiving 75 mu g vitamin A/d (P < 0.001) than in those receiv ing 37.5 mu g/d. The interaction of vitamin A deficiency and small int estinal injury may explain the efficacy of vitamin A supplementation i n preventing childhood diarrheal disease mortality in developing count ries, and highlights the need for ensuring adequate vitamin A status i n people worldwide with diseases and/or treatments which may injure th e gastrointestinal tract.