Influence of topical rectal application of drugs on dextran sulfate-induced colitis in rats.
A rat model of colitis [dextran sulfate (DSS)] was used to study the permeation of Evans blue (EB) from the lumen into the wall of proximal and distal colonic loops after exposure to the dye for 2 hr. Topical application of drugs used in human ulcerative colitis (lidocaine, mesalazine, prednisolone, or sucralfate) was given daily during induction of colitis to protect the mucosa. The mucosal changes were evaluated with special regard to peptidergic innervation [substance P (SP) and neuropeptide Y (NPY)], invasion of antigen-presenting polydendritic cells, and mucin-containing goblet cells. DSS-treatment caused a significantly increased permeation of EB. In the proximal loops a significant inhibition was obtained after treatment with lidocaine, prednisolone, or sucralfate. In the distal loops only treatment with lidocaine had a preventive effect. Immunocytochemically there was a clear hyperplasia of both mucosal SP- and NPY-immunoreactive nerve fibers in regions with crypt abnormalities. In these regions also most of the goblet cells were devoid of mucus. Like the changes in permeation, these morphological changes were most prominent in the distal loops. With induction of colitis, the mucosa and lamina propria were invaded by polydendritic cells; the visual score was markedly decreased in the proximal loops treated with lidocaine, prednisolone, or sucralfate. In the distal loops similar effects were obtained after treatment with lidocaine or prednisolone. Prevention of the influx of antigens in both loops after lidocaine treatment with reduced recruitment of polydendritic cells into the lamina propria is suggested. The nerve hyperplasia may thus be secondary to luminal challenge with antigens during induction of colitis. The discrepancy between increased permeation and absence of polydendritic cell response in the distal loops after prednisolone may reflect separate actions of steroids on the intestinal epithelium and the immune cells.
Björck
S
S
Department of Surgery, Sahlgren Hospital, Sweden.
Jennische
E
E
Dahlström
A
A
Ahlman
H
H
D000285:Administration, Rectal; D000636:Aminosalicylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000938:Antigen-Presenting Cells / Q000473:pathology; D002463:Cell Membrane Permeability / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D003093:Colitis, Ulcerative / Q000188:drug therapy; D003106:Colon / Q000737:chemistry / Q000187:drug effects / Q000294:innervation / Q000473:pathology; D004396:Coloring Agents; D016264:Dextran Sulfate; D005070:Evans Blue; D006801:Humans; D007150:Immunohistochemistry; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008012:Lidocaine / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D019804:Mesalamine; D009412:Nerve Fibers / Q000737:chemistry / Q000473:pathology; D009478:Neuropeptide Y / Q000032:analysis; D011239:Prednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000032:analysis; D013373:Substance P / Q000032:analysis; D013392:Sucralfate / Q000008:administration & dosage / Q000493:pharmacokinetics
D000636:Aminosalicylic Acids; D000779:Anesthetics, Local; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D004396:Coloring Agents; D009478:Neuropeptide Y; D009418:S100 Proteins; D013373:Substance P; D005070:Evans Blue; D019804:Mesalamine; D013392:Sucralfate; D016264:Dextran Sulfate; D008012:Lidocaine; D011239:Prednisolone