Changes in sulfated macromolecules produced in vivo during normal and indomethacin-delayed ulcer healing in rats

The aim of this study was to examine the synthesis of sulfated glycosaminoglycans during normal healing of experimental acetic acid-induced gastric ulcer in rats and to investigate the effect of indomethacin, a drug known to delay ulcer healing, on this synthesis using an in vivo labelling system. Analysis revealed the presence of two major sulfated species in control tissue; a population of sulfated mucins and glycosaminoglycans, predominantly galactosaminoglycans. The incorporation of [35S]sulfate label into glycosaminoglycans synthesized in the granulation tissue of healing ulcers increased significantly (P < 0.05) as compared to day 0 and control levels at day 14. Treatment of animals with indomethacin (1 mg/kg daily) resulted in a further significant (P < 0.01) rise in sulfated glycosaminoglycan synthesis in indomethacin-treated ulcer tissue compared to that found in healing ulcers at day 14. The increased glycosaminoglycan synthesis was due to increased levels of chondroitin sulfate and dermatan sulfate. Glycosaminoglycan synthesis is elevated at the ulcer site during healing of experimental gastric ulcers; however, indomethacin treatment, which delays ulcer healing, significantly increases the synthesis of glycosaminoglycans above that seen in healing ulcers. Changes in the sulfated glycosaminoglycan content of the ulcer may play a role in the healing process and may give further insight into the mechanisms by which indomethacin delays ulcer healing.