title: Ischemic preconditioning attenuates ischemia-reperfusion-induced mucosal apoptosis by inhibiting the mitochondria-dependent pathway in rat small intestine.
abstract: Ischemic preconditioning provides a way of protecting organs from damage inflicted with prolonged ischemia-reperfusion. In this study, we investigated the mechanism of ischemic preconditioning involved in inhibition of prolonged ischemia-reperfusion-induced mucosal apoptosis in rat small intestine. Ischemic preconditioning was triggered by a transient occlusion of the superior mesenteric artery followed by reperfusion. Ischemia-reperfusion was induced by 60-min occlusion of the superior mesenteric artery followed by 60-min reperfusion in the small intestine. Ischemia-reperfusion alone induced mucosal apoptosis and mitochondrial respiratory dysfunction via promoted reactive oxygen species generation, reduced mitochondrial glutathione oxidation, increased mitochondrial lipid peroxidation, reduced mitochondrial membrane potential, and enhanced release of cytochrome c from mitochondria to activate caspase-9 and caspase-6 in the small intestine. Pretreatment with 20-min ischemia followed by 5-min reperfusion significantly inhibited the prolonged ischemia-reperfusion-induced mucosal apoptosis by 30%. Ischemic preconditioning ameliorated mitochondrial respiratory dysfunction by 50%, reduced reactive oxygen species generation by 38%, and suppressed mitochondrial lipid peroxidation by 36%, resulting in improvement of the mitochondrial membrane potential and prevention of cytochrome c release as well as caspase-6 activation. Results suggest that ischemic preconditioning attenuated ischemia-reperfusion-induced mucosal apoptosis partly by inhibiting the reactive oxygen species-mediated mitochondria-dependent pathway in the rat small intestine.
authors.affiliation: Department of Internal Medicine, Saga Medical School, Saga 849-8501, Japan.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Akifumi
authors.initials: A
authors.lastname: Ootani
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Iwakiri
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fujise
authors.forename: Seiji
authors.initials: S
authors.lastname: Tsunada
authors.forename: Shuji
authors.initials: S
authors.lastname: Toda
authors.forename: Kazuma
authors.initials: K
authors.lastname: Fujimoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D045304:Cytochromes c / Q000378:metabolism; D004247:DNA / Q000302:isolation & purification; D053938:DNA Fragmentation; D004587:Electrophoresis, Agar Gel; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007421:Intestine, Small / Q000502:physiology*; D019194:Ischemic Preconditioning; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology*; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D045304:Cytochromes c; D004247:DNA