Effect of methotrexate on the intestinal mucosa of PGE2-treated rats

In the present study, we aimed to protect the intestinal mucosa from small bowel damage in methotrexate (MTX)-treated rats. The protective effect of prostaglandin E2 (PGE2) was investigated. Ileal integrity was evaluated making use of different biochemical parameters: content of sucrase and maltase activities, contents of DNA, proteins, AMPc, PGE2, putrescine (Put), spermine (Spm) and spermidine (Spd). Rats were orally administered 0.5 ml of NaCl solution (0.9%) containing or not containing 400 micrograms.ml-1 of PGE2 twice daily, during three or ten days. Half an hour after the 18th ingestion of PGE2, 0.5 ml of NaCl solution (0.9%) containing MTX (16 mg.ml-1) was injected intravenously. Rats were killed exactly 48 hours after this injection. MTX had no effect on the Put content, increased the AMPc content and decreased the contents of DNA, proteins, Spm, Spd, PGE2 and sucrase or maltase activity. PGE2 had no effect on the biochemical parameters we studied, except on the contents of DNA (10-day treatment) and of PGE2 (3- and 10-day treatment). When MTX was injected after PGE2 treatment, as compared with what was observed when MTX was used as reported above, we observed--an increase in spermine content after 3-day PGE2 treatment and- an increase in the contents of DNA, Spm, Spd and disaccharidase activity after 10-day PGE2 treatment. No other significant variation in the other biochemical parameters was recorded, whatever the duration of the PGE2 treatment. These results indicate that PGE2 could partially protect the intestinal mucosa against the biochemical effects of MTX. Other experimental conditions may need to be chosen in order to obtain a better cytoprotective effect of PGE.