The significance of removing oxygen-derived free radicals in the treatment of acute and chronic duodenal ulceration in the rat.
Rats infused for 24 h with pentagastrin (4 micrograms kg-1 min-1) and carbachol (0.8 microgram kg-1 min-1) developed acute duodenal ulceration (100%) and hyperchlorhydria (69 +/- 5.3 mumol h-1 vs 14 +/- 0.9 mumol h-1, P less than 0.001, n = 10). The animals were then given daily by gavage, saline, allopurinol with dimethyl sulphoxide (DMSO) or cysteine with methyl methionine sulphonium bromide (MMSB). Two days after the infusion, 10 rats (100%) given saline and 7 rats (70%) given allopurinol and DMSO, or cysteine and MMSB, showed duodenal ulceration. Five days after the infusion, 8 rats (80%) given saline, 3 rats (30%) given allopurinol and DMSO, and 2 rats (20%) given cysteine and MMSB had duodenal ulceration. Seven days after the infusion, only 5 rats (50%) given saline still had duodenal ulceration. Daily intramuscular injection of reserpine (0.1 mg kg-1) for 6 weeks produced chronic duodenal ulceration (90%) and hyperchlorhydria (47 +/- 3.1 mumol h-1 vs 12 +/- 0.9 mumol h-1, P less than 0.001, n = 10). Animals were then given daily by gavage, saline, allopurinol and DMSO, or cysteine and MMSB. Five days after reserpine, 10 rats (100%) given saline, 8 rats (80%) given allopurinol and DMSO, and 7 rats (70%) given cysteine and MMSB showed duodenal ulceration. Ten days after reserpine, 9 rats (90%) given saline, 3 rats (30%) given allopurinol and DMSO, and 4 rats (40%) given cysteine and MMSB had duodenal ulceration. Fifteen days after reserpine, 8 rats (80%) receiving saline and only one rat (10%) receiving allopurinol and DMSO or cysteine and MMSB had duodenal ulceration.(ABSTRACT TRUNCATED AT 250 WORDS)
Salim
A S
AS
University Department of Surgery, Royal Infirmary, Glasgow, UK.
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002217:Carbachol; D003545:Cysteine / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005609:Free Radicals; D005744:Gastric Acid / Q000378:metabolism; D008297:Male; D010418:Pentagastrin; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine
D000897:Anti-Ulcer Agents; D005609:Free Radicals; D000493:Allopurinol; D012110:Reserpine; D002217:Carbachol; D010418:Pentagastrin; D003545:Cysteine; D004121:Dimethyl Sulfoxide