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

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 corr elated the enhanced production of superoxide anion with increased lipid per oxidation, DNA fragmentation and membrane microviscosity, indices of oxidat ive 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-imm ersion 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 IS consecutive days. Similarly, half of the animals exposed to chr onic stress were pretreated orally with 100 mg GSPE/kg/day for 15 consecuti ve days. Acute stress produced maximal injury to both gastric mucosa and in testinal mucosa as compared to chronic stress. Acute stress and chronic str ess increased cytochrome c reduction by 12.2- and 4.8-fold, respectively, i n the gastric mucosa, and 12.1- and 4.6-fold in the intestinal mucosa. Acut e stress increased lipid peroxidation, DNA fragmentation and membrane micro viscosity 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 dec reased acute stress-induced lipid peroxidation, DNA fragmentation and membr ane 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 microv iscosity 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 d ecreased chronic stress-induced lipid peroxidation, DNA fragmentation and m embrane microviscosity by 23%, 21% and 25%, respectively, in the gastric mu cosa, and by 26%, 26% and 25%, respectively, in the intestinal mucosa. Thes e results demonstrate that acute stress and chronic stress can induce gastr ointestinal oxidative stress and mucosal injury through enhanced production of ROS, and that GSPE provides significant protection against gastrointest inal oxidative stress and mucosal injury by scavenging these ROS. (C) 1999 Elsevier Science Inc.