The Intestinal Absorption of 3‐O‐Methyl‐D‐glucose in Methotrexate‐Treated Rats

Abstract

SummaryThe in vivo absorption of 3–0‐methyl‐D‐glucose (3MG) as a marker of intestinal function has not been studied in an animal model. We evaluated the use of 3MG as a marker of intestinal absorption when given en‐terally to rats recovering from small bowel mucosal injury induced by methotrexate (MTX). Radiolabeled 3MG was administered into the duodenum of control (CON) and MTX‐treated rats and blood samples were obtained at specified intervals. Mucosal permeability was also assessed using radiolabeled mannitol and polyethylene glycol 900 (PEG). Concentration time points were plotted, and area under the curve was calculated as an approximation of absorbed dose. Mucosal weight, maltase activity, and protein content were determined on mucosal scrapings. During the acute phase (day 5), 3MG absorption and maltase‐specific activity were significantly decreased in the MTX group when compared to the CON group (p < 0.001). The MTX group showed a trend toward greater permeability to mannitol when compared to the CON group; however, this was not statistically significant. Mucosal permeability to PEG was similar in both groups. During a later stage in the recovery process (day 12), the area under the curve calculations for 3MG absorption were the same for both CON and MTX animals, with maltase activity in the MTX group recovering to control values. Changes in 3MG absorption paralleled total maltase activities following severe injury. These results suggest that the combined active and passive transport of 3MG in vivo could be of use as a marker of intestinal absorption in states where the small intestine has sustained major damage resulting in compromised absorption as well as brush border digestion.