Role of oxygen-derived free radicals in mechanism of acute and chronic duodenal ulceration in the rat.

This study employed the oxygen-derived free radical removing agents DL-cysteine, methyl-methionine sulfonium bromide (MMSB), dimethyl sulfoxide (DMSO), and allopurinol to examine the role of oxyradicals in the mechanism of acute and chronic duodenal ulceration in the rat. These agents were administered by gavage under light ether anesthesia. All rats infused subcutaneously for 24 hr with pentagastrin (4 micrograms/kg/min) and carbachol (0.8 microgram/kg/min) developed acute duodenal ulceration and hyperchlorhydria (68 +/- 6.1 mumol vs 12.5 +/- 0.3 mumol, mean +/- SEM, N = 10, P less than 0.001). Pretreatment with DL-cysteine, MMSB, DMSO, or allopurinol provided dose-dependent protection against this ulceration without significantly influencing the hyperchlorhydria. One percent solutions of these agents protected at least 20% of rats against ulceration. Five or 10% solutions of DL-cysteine, MMSB, or DMSO protected at least 70% of rats against ulceration and similar concentrations of allopurinol protected all animals. All rats having intramuscular reserpine (0.1 mg/kg) every day for six weeks developed chronic duodenal ulceration and hyperchlorhydria (52 +/- 3.1 mumol vs 13.1 +/- 0.7 mumol, mean +/- SEM, N = 10, P less than 0.001). Pretreatment with DL-cysteine, MMSB, DMSO, or allopurinol achieved dose-dependent protection against ulceration without significantly influencing the hyperchlorhydria. One percent solutions of DL-cysteine, MMSB, or DMSO protected at least 60% of rats against ulceration; however, a similar concentration of allopurinol protected 80% of animals. Five or 10% solutions of DL-cysteine, MMSB, or DMSO protected at least 80% of rats against ulceration and similar concentrations of allopurinol protected all rats.(ABSTRACT TRUNCATED AT 250 WORDS)