New ulcerative colitis model induced by sulfhydryl blockers in rats and the effects of antiinflammatory drugs on the colitis.
We tried to produce a new ulcerative colitis model in rats by topical administration of sulfhydryl blockers. After male SD rats were fasted for 24 hr, 100 microliters of 3% N-ethylmaleimide (NEM) or iodoacetamide (IA) was introduced into the colon via a Nelaton's catheter. Both NEM and IA caused severe diarrhea with rectal bleeding and decreased body weight for about 7 days. At autopsy, adhesions and dilatation of the colon and severe mucosal lesions were observed. Both the weight and myeloperoxidase activity of the colon increased markedly. Maximum changes were observed within 1-3 days followed by gradual recovery, but even on day 21, some abnormalities were still observed. The ulceration and inflammation of the colon were confirmed by histological studies. Antiinflammatory drugs such as indomethacin inhibited the inflammation of the colon by NEM, but aggravated the ulceration. These results revealed that sulfhydryl blockers instilled into the colon caused ulcerative colitis in the rat. This model may be useful in studies on the pathogenesis of ulcerative colitis and the evaluation of drugs for therapy. Furthermore, it was suggested that antiinflammatory drugs may delay the healing of colonic ulcers.
Satoh
H
H
Pharmaceutical Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Sato
F
F
Takami
K
K
Szabo
S
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D016227:Benzoquinones / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D003093:Colitis, Ulcerative / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D005033:Ethylmaleimide / Q000008:administration & dosage / Q000633:toxicity*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000188:drug therapy; D007213:Indomethacin / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007460:Iodoacetamide / Q000008:administration & dosage / Q000633:toxicity*; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013439:Sulfhydryl Reagents / Q000008:administration & dosage / Q000633:toxicity*
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D016859:Lipoxygenase Inhibitors; D013439:Sulfhydryl Reagents; D003907:Dexamethasone; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D009195:Peroxidase; D005033:Ethylmaleimide; D007213:Indomethacin; D007460:Iodoacetamide