Acute and chronic stress-induced oxidative gastrointestinal injury in rats, and the protective ability of a novel grape seed proanthocyanidin extract

Abstract

Reactive oxygen species (ROS) are implicated in the pathogenesis of stress-induced gastrointestinal injury. In the present study, we have investigated the effects of acute stress and chronic stress on the enhanced production of superoxide anion as determined by cytochrome c reduction assay, and correlated the enhanced production of superoxide anion with increased lipid peroxidation, DNA fragmentation and membrane microviscosity, indices of oxidative tissue injury, in gastric mucosa and intestinal mucosa, and determined the protective effects of a novel IH636 grape seed proanthocyanidin extract (GSPE) against mucosal injury. Acute stress was induced by water-immersion restraint stress for 90 min, while chronic stress was induced by water-immersion restraint stress for 15 min/day for 15 consecutive days. Half of the animals exposed to acute stress were pretreated orally with 100 mg GSPE/kg/day for 15 consecutive days. Similarly, half of the animals exposed to chronic stress were pretreated orally with 100 mg GSPE/kg/day for 15 consecutive days. Acute stress produced maximal injury to both gastric mucosa and intestinal mucosa as compared to chronic stress. Acute stress and chronic stress increased cytochrome c reduction by 12.2- and 4.8-fold, respectively, in the gastric mucosa, and 12.1- and 4.6-fold in the intestinal mucosa. Acute stress increased lipid peroxidation, DNA fragmentation and membrane microviscosity by 3.3-, 4.1- and 11.6-fold, respectively, in the gastric mucosa, and 4.4-, 5.2- and 16.6-fold, respectively, in intestinal mucosa. GSPE decreased acute stress-induced lipid peroxidation, DNA fragmentation and membrane microviscosity by 15%, 12% and 13%, respectively, in the gastric mucosa, and by 13%, 14% and 16%, respectively, in the intestinal mucosa. Chronic stress increased lipid peroxidation, DNA fragmentation and membrane microviscosity by 2.9-, 3.3- and 6.3- fold, respectively, in the gastric mucosa, and 3.3-, 4.2- and 9.3-fold, respectively, in the intestinal mucosa. GSPE decreased chronic stress-induced lipid peroxidation, DNA fragmentation and membrane microviscosity by 23%, 21% and 25%, respectively, in the gastric mucosa, and by 26%, 26% and 25%, respectively, in the intestinal mucosa. These results demonstrate that acute stress and chronic stress can induce gastrointestinal oxidative stress and mucosal injury through enhanced production of ROS, and that GSPE provides significant protection against gastrointestinal oxidative stress and mucosal injury by scavenging these ROS.