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.

Upregulation of TLR4 mRNA Expression Levels in Broiler Chickens Under Acute Heat Stress

“…Due to global warming, environmental temperatures are predicted to increase over the next decades, likely contributing to an increase in heat stress-induced organ injury and dysfunction during HS in animals (Yu et al, 2013). This study investigated the effect of AHS on the TLR4 mRNA expression levels in the liver, kidney, spleen, heart and small intestine of broiler chickens.…”

“…In addition, data from HS and endotoxin shock models (Ryan et al, 1994) support the critical role of the liver in the response to thermal and endotoxin challenge. During HS, a disturbance in the microecological balance of the intestinal flora may cause bacterial translocation and induce the production of intestinal endotoxins (Gu et al, 2012;Yu et al, 2013), allowing large amounts of endotoxins to reach the liver. TLR4 is stably expressed on the surface of many cells, including the Kupffer cells of the liver (Zuo et al, 2003).…”

Genome-Wide Transcriptional Analysis Reveals the Protection against Hypoxia-Induced Oxidative Injury in the Intestine of Tibetans via the Inhibition of GRB2/EGFR/PTPN11 Pathways

“…Especially for the first point, hypoxic pressure affects basic metabolic processes and produces high-level ROS, which lead to the increase of oxidative stress [49, 50]. Oxidative stress is an important contributor for tissue injuries, including intestine injury [18, 51]. …”

“…For example, increased oxidative stress induces the damage in the small intestine of male Sprague-Dawley rats by activating the pathway of p38 mitogen-activated protein kinase [18]. Another example, ischemia/reperfusion results in oxidative injury in animal's intestine.…”

Suppressed expression of mitogen-activated protein kinases in hyperthermia induced defective neural tube

“…It has been reported that extracellular HMGB1 could activate MAPKs and transduce the signal inside neural and gliocyte cells [14]. Yu et al found that heat stress could activate MAPKs signaling pathways [15]. The present study aims to investigate whether HMGB1 contributes to hyperthermia-induced NTDs through MAPKs pathway.…”