Anti-inflammatory effect of diosmectite in hapten-induced colitis in the rat.
1. Diosmectite is a natural silicate effectively used in the treatment of infectious diarrhoea. Its antidiarrhoeal properties involve adsorption of toxins and bacteria and modifications of the rheological characteristics of gastrointestinal mucus. Hence, the aim of this study was to test the intestinal anti-inflammatory activity of diosmectite. 2. Diosmectite (500 mg x kg(-1) day(-1), p.o.) was administered as a post-treatment to rats with chronic trinitrobenzene sulphonic acid colitis. Colonic status was checked 1 and 2 weeks after colitis induction by macroscopic, histological and biochemical examination. 3. Diosmectite post-treatment resulted in amelioration of the morphological signs (intestinal weight, macroscopic damage, necrosed area, histology) and biochemical markers (myeloperoxidase activity, glutathione levels, MUC2 expression, inducible nitric oxide synthase and interleukin-1beta (IL-1beta) and leukotriene B(4) synthesis), as well as in the reduction of the severity of diarrhoea. The effect of the clay was comparable to that of sulphasalazine (50 mg x kg(-1) day(-1)). 4. 5. Diosmectite exhibited a dose-dependent capacity to adsorb proteins in vitro as well as a dose-dependent inhibitory effect on the basolateral secretion of IL-8 by lipopolysaccharide (LPS)-stimulated HT29 cells. Diosmectite had a dose-dependent inhibitory effect on IL-1beta production by LPS-stimulated THP-1 cells. 6. The effect of diosmectite on MUC2 was post-transcriptional, since mRNA levels were unaffected. However, diosmectite is able to upregulate MUC2 mRNA levels in HT29-MTX cells. 7. Diosmectite has anti-inflammatory activity administered as a post-treatment. Possible mechanisms include adsorption of luminal antigens, increase of colonic mucin levels and possibly a direct modulatory action of cytokine production by mucosal cells.
Departments of Pharmacology, School of Pharmacy, University of Granada, Spain.
Raquel
R
González
Fermin Sánchez
FS
de Medina
Olga
O
Martínez-Augustin
Ana
A
Nieto
Julio
J
Gálvez
Severiano
S
Risco
Antonio
A
Zarzuelo
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002460:Cell Line / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006241:Haptens; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D053583:Interleukin-1beta; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007975:Leukotriene B4 / Q000378:metabolism; D009077:Mucins / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017640:Silicates / Q000627:therapeutic use*; D014302:Trinitrobenzenesulfonic Acid
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D006023:Glycoproteins; D006241:Haptens; D007375:Interleukin-1; D053583:Interleukin-1beta; D009077:Mucins; D010446:Peptide Fragments; D017640:Silicates; C052994:interleukin-1beta (163-171); D007975:Leukotriene B4; D014302:Trinitrobenzenesulfonic Acid; C033214:Smectite; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005978:Glutathione