Sources of superoxide radicals involved in the pathogenesis of diethyldithiocarbamate-induced gastric antral ulcer in rats.

The production of superoxide radicals as a result of decreased Cu,Zn-superoxide dismutase activity is considered to be the most important factor in the pathogenesis of diethyldithiocarbamate (DDC)-induced gastric antral ulcers in rats. The aim of the present study was to identify possible sources of superoxide radicals and the role of platelet-activating factor (PAF) in DDC-induced ulcer formation. Groups of rats were pretreated with a drug or antiserum before DDC (800 mg/kg) administration. The size of the DDC-induced gastric antral ulcers was measured. Pretreatment with anti-rat polymorphonuclear leukocyte serum or CV-3988 (a specific antagonist of PAF) 20 mg/kg significantly reduced the size of DDC-induced gastric antral ulcers. The results confirmed that superoxide radicals play an important role in the pathogenesis of DDC-induced gastric ulcer in rats and suggested that NADPH (reduced nicotinamide-adenine dinucleotide phosphate) oxidase in PAF-activated polymorphonuclear leukocytes may be involved in the generation of these radicals.