Protective effect of thiaton, an antispasmodic drug, against indomethacin-induced intestinal damage in rats.
The effect of thiaton [3-(di-2-thienylmethylene)-5-methyl-trans-quinolizidinium bromide], an antispasmodic drug, on indomethacin-induced intestinal damage was examined in rats. The animals were given indomethacin, s.c., and the intestinal mucosa was examined 24 h later. Thiaton or atropine was given s.c. twice, 30 min before and 8 h following indomethacin. Indomethacin caused intestinal damage, accompanied with increase in enterobacterial translocation as well as inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) activities, and these changes were significantly prevented by supplementation with 16,16-dimethyl prostaglandin E2 (dmPGE2). Treatment of the animals with thiaton dose-dependently prevented the intestinal damage, together with the suppression of MPO and iNOS activities, and these effects were similarly observed by atropine. The increase of bacterial translocation was also significantly prevented by both thiaton and atropine, similar to dmPGE2. Indomethacin enhanced intestinal motility, and this effect was inhibited by either thiaton, atropine or dmPGE2. The intestinal mucus and fluid secretions were decreased by indomethacin but enhanced by dmPGE2. Both thiaton and atropine slightly decreased these secretions under basal conditions but significantly reversed the decrease in the secretions caused by indomethacin. These results suggest that thiaton protects the small intestine against indomethacin-induced damage and inflammatory changes, and this effect is related with prevention of enterobacterial translocation, the process being associated with inhibition of intestinal hypermotility caused by indomethacin, probably due to anti-muscarinic action.
Kunikata
Tomonori
T
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Japan.
Miyazawa
Tohru
T
Kanatsu
Kenji
K
Kato
Shinichi
S
Takeuchi
Koji
K
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects; D007213:Indomethacin / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010276:Parasympatholytics / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D010276:Parasympatholytics; D011459:Prostaglandins E, Synthetic; D011807:Quinolizines; C030950:thiaton; D001285:Atropine; D019001:Nitric Oxide Synthase; D007213:Indomethacin