EFFECT OF DEHYDROLEUCODINE IN EXPERIMENTAL COLITIS IN RATS AND MICE

• Published in: Pharmacological research Vol. 40; no. 4; pp. 339 - 344
• Main Authors: WENDEL, G.H., MARIA, A.O.M., MOHAMED, F., DOMINGUEZ, S., SCARDAPANE, L., GIORDANO, O.S., GUERREIRO, E., GUZMAN, J.A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.10.1999
• Subjects: Acetic Acid; Animals; Anti-Ulcer Agents - therapeutic use; Colitis - chemically induced; Colitis - drug therapy; Colon - drug effects; Colon - pathology; Diarrhea - drug therapy; experimental colitis, dehydroleucodine, acetic acid; Irritants; Lactones - therapeutic use; Male; Mice; Organ Size - drug effects; Rats; Rats, Wistar; Sesquiterpenes - therapeutic use; Trinitrobenzenesulfonic Acid; experimental colitis, dehydroleucodine, acetic acid
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1006/phrs.1999.0521

Dehydroleucodine (DhL), a sesquiterpene lactone (SQL) of the guaianolide type isolated fromArtemisia douglasiana Besser, shows a pharmacological cytoprotective effect and significantly prevents the formation of gastric and duodenal lesions induced by various necrotising agents in rodents. The effects of DhL, on two models of experimental colitis were examined. Colitis was produced in male Wistar rats by rectal instillation of 5 and 10% acetic acid, following the methods of Eliakim et al. and Le Duc et al., respectively. In mice colitis was produced by rectal instillation of 0.1 ml of 2,4,6-trinitrobenzene sulphonic acid (5 mg in 50% ethanol) (TNB) as previously described by Chinet al . In this study, the administration of DhL 40 mg kg−1(1 h before the induction of colitis) significantly decreased mucosal damage. This effect was consistent in both models. The protection provided by DhL was accompanied by significant decreases in diarrhoea and colon weight; and histologically normal mucosa without ulceration and mucus production were observed. This study shows that both TNB and acetic acid colitis can be pharmacologically controlled by DhL. Our results suggest that the protective activity of DhL in experimental colitis is mediated, at least in part, through the increase of glycoprotein synthesis, anti-inflammatory effect and inhibition of COX-2 induction, and by inhibiting the degranulation of cells containing monoamines.