5-ASA-GLUTAMATE PROTECTS RATS FROM INFLAMMATORY BOWEL-DISEASE INDUCEDBY INTRACOLONIC ADMINISTRATION OF TRINITROBENZENSULFONIC ACID

Citation
C. Clerici et al., 5-ASA-GLUTAMATE PROTECTS RATS FROM INFLAMMATORY BOWEL-DISEASE INDUCEDBY INTRACOLONIC ADMINISTRATION OF TRINITROBENZENSULFONIC ACID, Italian Journal of Gastroenterology and Hepatology, 30(4), 1998, pp. 385-390
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenterology & Hepatology
ISSN journal
1125-8055
Volume
30
Issue
4
Year of publication
1998
Pages
385 - 390
Database
ISI
SICI code
1125-8055(1998)30:4<385:5PRFIB>2.0.ZU;2-O
Abstract
Background and aims. A new aminoacid derivative of 5-aminosalicylic ac id, 5-ASA-glutamate, releases 5-aminosalicylic acid independently of t he action of bacterial azore-ductases or adapt intestinal pH. In this study, 5-ASA-glutamate was compared with sulphasalazine with respect t o: I) therapeutic action, 2) effects on the synthesis of eicosanoids, 3) regional release of 5-aminosalicylic acid in the intestine. Methods . Colitis was induced in 29 rats by intracolonic administration of tri nitrobenzensulfonic acid. Nine animals received an equal amount of sal ine. Three days after induction of colitis, animals were randomly assi gned to equimolecular doses of 5-aminosalicylic acid as sulphasalazine (1040 mg/kg bw day) or 5-ASA-glutamate (850 mg/kg bw day) or arabic g um in water given intragastrically. Arabic gum was also administered t o animals that had received a saline enema (control group). The guts o f 3 rats from the 5-ASA-glutamate group and 3 from the sulphasalazine group were used to assess regional release of 5-ASA, while in all the others, after 21 days of treatment, macroscopic and histologic lesions were assessed and eicosanoids and leukotriene determinations were per formed. Results. The 5-ASA-glutamate group had macroscopic (2.20+/-0.5 8) and histologic (2.80+/-1.24) significantly lower scores than the tr initrobenzensulfonic acid group (3.40+/-0.22 and 6.50+/-1.2 respective ly). 5-ASA-glutamate group had reduced PGE(2) (-31%) and TXB2 (-25%) m ore effectively than the sulphasalazine group. LTB4 release was not af fected by 5-ASA-glutamate treatment while sulphasalazine produced a no n significant, but quite consistent, reduction in LTB4 release (-37%). The release of 5-ASA after sulphasalazine was higher in the small int estine, lower in the colon compared to that following 5-ASA-glutamate administration. Conclusions. 5ASA-glutamate was effective in reducing the macroscopic and histologic score in the trinitrobenzensulfonic aci d induced colitis. It also had some effect in reducing eicosanoid synt hesis and could be a promising drug for the treatment of inflammatory bowel disease.