Prevention of indomethacin-induced acute gastric mucosal injury by spermine in the rat.
The effect of spermine tetrahydrochloride was investigated on the indomethacin-induced acute mucosal injury and mucosal lipid peroxidation in rats. Spermine was given orally at doses of 25, 75 and 150 mg/kg and, intraperitoneally at 10, 25 and 50 mg/kg 1 hour before 25 mg/kg indomethacin administration. Macroscopic injury was measured by the use of a stereomicroscope. Mucosal malondialdehyde (MDA) levels were determined by an HPLC method. Oral spermine reduced dose-dependently the extent of macroscopic injury from 22.87 +/- 2.88 mm to 11.8 +/- 2.48 mm (p < 0.01, 25 mg/kg), 6.53 +/- 4.19 mm (p < 0.0007, 75 mg/kg) and 0.25 +/- 0.25 mm (p < 0.0001,150 mg/kg). Intraperitoneally administered spermine prevented dose-dependently the indomethacin produced lesions from 19.25 +/- 4.31 mm to 12.63 +/- 3.18 mm (p < 0.01, 25 mg/kg) and to 0.33 +/- 0.33 mm (p < 0.001, 50 mg/kg). Doses necessary for intraperitoneal protection were lower than those achieving similar effect, orally suggesting different mechanisms of action. Neither oral or intraperitoneal spermine influenced the mucosal MDA levels.
Buzás
G
G
J. Balassa Hospital, Department of Gastroenterology, Budapest, Hungary.
Demel
Z
Z
Józan
J
J
Hamar
J
J
D000208:Acute Disease; D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects*; D007213:Indomethacin / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000494:pharmacology*; D013272:Stomach Diseases / Q000139:chemically induced
D013096:Spermine; D007213:Indomethacin