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

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Abstract
This study employed the oxygen-derived free radical removing agentsdl -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 μg/kg/min) and carbachol (0.8 μg/kg/min) developed acute duodenal ulceration and hyperchlorhydria (68 ±6.1 μmol vs 12.5±0.3 μmol, mean±sem, N=10, P<0.001). Pretreatment withdl-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 ofdl-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 μmol vs 13.1±0.7 μmol, mean±sem, N=10, P<0.001). Pretreatment withdl -cysteine, MMSB, DMSO, or allopurinol achieved dose-dependent protection against ulceration without significantly influencing the hyperchlorhydria. One percent solutions ofdl -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 ofdl -cysteine, MMSB, or DMSO protected at least 80% of rats against ulceration and similar concentrations of allopurinol protected all rats. This study shows that in the rat oxygen-derived free radicals are directly implicated in the mechanism of secretagogue-induced acute and chronic duodenal ulceration and that removing these radicals protects the duodenum against ulceration.