Rotenone, a mitochondrial electron transport inhibitor, ameliorates ischemia-reperfusion-induced intestinal mucosal damage in rats.
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.
Ichikawa
Hiroshi
H
Department of Food Sciences and Nutritional Health, The Faculty of Human Environment, Kyoto Prefectural University, Kyoto, Japan. hichik@kpu.ac.jp
Takagi
Tomohisa
T
Uchiyama
Kazuhiko
K
Higashihara
Hiroshi
H
Katada
Kazuhiro
K
Isozaki
Yutaka
Y
Naito
Yuji
Y
Yoshida
Norimasa
N
Yoshikawa
Toshikazu
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016207:Cytokines / Q000032:analysis; D004579:Electron Transport / Q000187:drug effects*; D006454:Hemoglobins / Q000032:analysis; D007413:Intestinal Mucosa / Q000098:blood supply / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D007421:Intestine, Small / Q000098:blood supply / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy*; D012402:Rotenone / Q000494:pharmacology*; D013386:Succinates / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D000975:Antioxidants; D016207:Cytokines; D006454:Hemoglobins; D013386:Succinates; D017392:Thiobarbituric Acid Reactive Substances; D012402:Rotenone; D009195:Peroxidase