Direct cytotoxic effect of oxygen radicals on the gastric mucosa

Oxygen radical release has been proposed as a pathogenetic factor in the formation of acute gastric mucosal injury. We assessed the ability of the naturally occurring oxygen radical generating system hypoxanthine/xanthine oxidase (HX/XO) to cause gross gastric mucosal injury and measured the effect on regional mucosal blood flow. Local intra-arterial infusion of HX/XO into the vascular network of the stomach caused marked gross mucosal injury in the antrum and corpus. This injury occurred even in the absence of exogenous luminal acid and was aggravated by luminal acidification with 1 ml of 0.1N HCl. The selective oxygen radical scavenger superoxide dismutase (SOD) prevented mucosal injury caused by HX/XO. The effects of HX/XO and SOD were not mediated by alterations in regional gastric mucosal blood flow, as measured by the radiolabeled microspheres and reference sample method. These findings suggest that oxygen radicals are capable of causing substantial gastric mucosal injury by a direct cytotoxic effect independent of luminal acid or mucosal blood supply and give support to the concept that oxygen radical release may be a major primary pathogenetic factor in the development of acute gastric mucosal injury.