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Repeated administration of diethyldithiocarbamate (DDC: 750 mg/kg, s.c.), a superoxide dismutase (SOD) inhibitor, to fed rats induced ulcers in the duodenum with less lesion in the stomach. DDC not only reduced basal acid output but also impaired duodenal alkaline secretion under both basal and acid-stimulated conditions. The duodenal ulcers induced by DDC were significantly prevented by either allopurinol, SOD or dmPGE2 at the doses which significantly reversed the inhibited alkaline responses caused by DDC. The pathogenesis of DDC-induced duodenal ulcers may involve impairment of duodenal alkaline secretion, probably caused by insufficiency of antioxidant machinery in the mucosa.
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