Protective effect of geranylgeranylacetone against loxoprofen sodium-induced small intestinal lesions in rats.
Nonsteroidal anti-inflammatory drugs induce small intestinal ulcers but the preventive measures against it remain unknown. So we evaluated the effect of geranylgeranylacetone (GGA), a mucosal protectant, on both the mucus content and loxoprofen sodium-induced lesions in the rat small intestine. Normal male Wistar rats were given GGA (200 or 400mg/kg p.o.) and euthanized 3h later for measurement of mucin content and immunoreactivity. Other Wistar rats were given loxoprofen sodium (30mg/kg s.c.) and euthanized 24h later. GGA (30-400mg/kg p.o.) was administered twice: 30min before and 6h after loxoprofen sodium. The total mucin content of the small intestinal mucosa increased, especially the ratio of sialomucin, which increased approximately 20% more than the control level after a single dose of GGA. Loxoprofen sodium provoked linear ulcers along the mesenteric margin of the distal jejunum, accompanied by an increase in enterobacterial translocation. Treatment of the animals with GGA dose-dependently prevented the development of intestinal lesions, and bacterial translocation following loxoprofen sodium was also significantly decreased. GGA protects the small intestine against loxoprofen sodium-induced lesions, probably by inhibiting enterobacterial invasion of the mucosa as a result of the increase in the mucosal barrier.
Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan.
Tomohisa
T
Iwai
Takafumi
T
Ichikawa
Mitsuhiro
M
Kida
Yukinobu
Y
Goso
Makoto
M
Kurihara
Wasaburo
W
Koizumi
Kazuhiko
K
Ishihara
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004224:Diterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004755:Enterobacteriaceae / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010666:Phenylpropionates; D051381:Rats; D017208:Rats, Wistar; D052116:Sialomucins / Q000378:metabolism; D014456:Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D004224:Diterpenes; D010666:Phenylpropionates; D052116:Sialomucins; C040656:loxoprofen; C031049:geranylgeranylacetone