Possible protective effects of exogenous
melatonin on colonic
inflammation were studied in rats.
Colitis was induced by intracolonic (i.c.) instillation of 4%
acetic acid (AA) and the resulting injury was assessed after 1 and 48 hr. Diffuse
hyperemia and
bleeding with erosions and ulcerations were observed in the colons of vehicle-treated rats.
Melatonin administered in doses of 5 and 10 mg/kg reduced significantly the extent of gross mucosal damage after intraperitoneal as well as i.c. dosing. The
inflammation induced increase in colonic wet weight was also reduced by
melatonin treatment. In the early phase of colonic
inflammation (60 min),
melatonin partly prevented the decrease of
reduced glutathione (GSH) content and limited lysosomal
enzyme, N-acetyl-
glucosaminidase and
cathepsin D, activities induced by AA, with no changes in
proteins or
acid phosphatase activity. Increase of
myeloperoxidase activity (MPO) caused by colonic
inflammation was prevented by
melatonin given i.c. As observed 48 hr after AA exposure, there was no difference between the effect of vehicle and
melatonin on the content of GSH.
Colitis did not influence the
melatonin content of the colon. After administration of exogenous
melatonin, plasma, pineal and gut
melatonin tended to increase. The results indicate that
melatonin participates in various defense mechanisms against colonic inflammatory processes by preserving the important
endogenous antioxidant reserve of GSH, by preventing lysosomal
enzyme disruption, by inhibiting enhanced MPO activity, thus reducing the extent of colonic damage, mainly in the early phase of
colitis.