In
ischemia-reperfusion (I/R)-induced tissue injury,
oxygen radicals can be generated by several mechanisms. One of the important sources of
oxygen radicals is thought to be mitochondrial respiration. The aim of this study was to investigate the antioxidative defense effect of the mitochondrial electron transport inhibitor,
rotenone using the I/R-induced rat intestinal mucosal injury model in vivo. Intestinal
ischemia was induced for 30 min by applying a small clamp to the superior mesenteric artery in rats.
Rotenone at a dose of 100 mg/kg was given to rats orally 2 h before the
ischemia. Intraluminal
hemoglobin and
protein levels, the mucosal content of
thiobarbituric acid-reactive substances (
TBARS), the mucosal
myeloperoxidase activity, and the content of inflammatory
cytokines (CINC-1, TNF-alpha) were all significantly increased from mean basal levels after 60 min of reperfusion. These increases after I/R were inhibited by treatment with
rotenone at a dose of 100 mg/kg. Co-administration with
succinate (100 mg/kg), a substrate of the mitochondrial electron transport system, cancelled significant reduction of intraluminal
hemoglobin and mucosal
TBARS treated with
rotenone alone. The results of the present study indicate that
rotenone inhibited lipid peroxidation and reduced development of the intestinal mucosal
inflammation induced by I/R in rats. This investigation suggests that
rotenone has potential as a new therapeutic agent for
reperfusion injury.