title: Involvement of oxidative stress and mitogen-activated protein kinase signaling pathways in heat stress-induced injury in the rat small intestine.
abstract: Extreme heat stress-induced gastrointestinal injury and dysfunction may occur during summer. We investigated possible mechanisms of heat stress-induced damage in the small intestine using male Sprague-Dawley rats subjected to 2 h of heat stress (40 °C, 60% relative humidity) daily for 10 consecutive days. Rats were killed at specific times immediately following heat treatment to determine: morphological changes by optical and electron microscopy; intestinal permeability using fluorescein isothiocyanate-dextran; production of reactive oxygen species (ROS), malondialdehyde (MDA), and activities of superoxide-dismutase and glutathione-peroxidase by specific assays; phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) by immunocytochemistry and western-blot analysis. The rat intestinal epithelial cell line (IEC-6) and specific MAPK inhibitors were used for in vitro investigation of effects of activation of MAPKs by heat stress. Heat stress caused marked morphological damage to the small intestine and significantly increased intestinal permeability. Heat stress increased ROS and MDA production, and significantly reduced anti-oxidase activity. MAPK activity in small intestine was increased by heat stress. In vitro, heat stress caused damage and apoptosis in IEC-6 cells; inhibition of ERK1/2 activation (by U0126) exacerbated these effects, which were attenuated by inhibition of JNK (by SP600125) and p38 (by SB203580) activation. Hence, heat stress caused severe small intestine injury, increased oxidative stress, and activated MAPK signaling pathways. The in vitro studies indicated that ERK1/2 activation is anti-apoptotic, and JNK and p38 activation are pro-apoptotic in heat stressed intestinal epithelial cells.
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yu
authors.forename: Fenghua
authors.initials: F
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Yin
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Weili
authors.initials: W
authors.lastname: Luan
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Hou
authors.forename: Yougang
authors.initials: Y
authors.lastname: Zhong
authors.forename: Dan
authors.initials: D
authors.lastname: Jia
authors.forename: Junlan
authors.initials: J
authors.lastname: Zan
authors.forename: Wuren
authors.initials: W
authors.lastname: Ma
authors.forename: Banchao
authors.initials: B
authors.lastname: Shu
authors.forename: Jianqin
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001831:Body Temperature / Q000502:physiology; D002460:Cell Line; D018882:Heat Stress Disorders / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000473:pathology / Q000503:physiopathology*; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D012881:Skin Temperature / Q000502:physiology
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D008084:Lipoxygenase; D020928:Mitogen-Activated Protein Kinases