Selected Contribution: Hyperthermia-induced intestinal permeability and the role of oxidative and nitrosative stress

Abstract

-The purpose of this study was to characterize intestinal permeability changes over a range of physiologically relevant body temperatures in vivo and in vitro. Initially, FITC-dextran (4,000 Da), a large fluorescent molecule, was loaded into the small intestine of anesthetized rats. The rats were then maintained at ϳ37°C or heated over 90 min to a core body temperature of ϳ41, ϳ41.5, or ϳ42.5°C. Permeability was greater in the 42.5°C group compared with the 37, 41, or 41.5°C groups. Histological analysis revealed intestinal epithelial damage in heated groups. Everted intestinal sacs were then used to further characterize hyperthermia-induced intestinal permeability and to study the potential role of oxidative and nitrosative stress. Increased permeability to 4,000-Da FITC-dextran in both small intestinal and colonic sacs was observed at a temperature of 41.5-42°C compared with 37°C, along with widespread intestinal epithelial damage. Administration of antioxidant enzyme mimics or a nitric oxide synthase inhibitor did not reduce permeability due to heat stress, and tissue concentrations of a lipid peroxidation product were not altered by heat stress, suggesting that oxidative and nitrosative stress were not likely mediators of this phenomenon in vitro. In conclusion, hyperthermia produced increased permeability and marked intestinal epithelial damage both in vivo and in vitro, suggesting that thermal disruption of epithelial membranes contributes to the intestinal barrier dysfunction manifested with heat stress. intestine; heat stress; free radicals; nitric oxide; FITC-dextran

Effects of supplemental zinc amino acid complex on gut integrity in heat-stressed growing pigs

“…Interestingly, almost all aspects of intestinal integrity deteriorated from days 1 to 7 of HS (Table 2) and this suggests that acclimation (from a production perspective) is partially independent of HS-induced intestinal barrier dysfunction. Heat-stressed animals divert blood flow from the viscera to the periphery in an attempt to maximize heat dissipation (Lambert et al, 2002), which in addition to hyperthermia leads to intestinal hypoxia (Hall et al, 1999). Enterocytes are particularly sensitive to hypoxia and nutrient restriction (Rollwagen et al, 2006), resulting in ATP depletion, and increased oxidative and nitrosative stress (Hall et al, 2001).…”

“…For instance, the small intestine is highly sensitive to heat damage (Kregel, 2002), and is one of the first tissues up-regulating heat shock proteins during hyperthermia (Flanagan et al, 1995). HS increases intestinal permeability (Lambert et al, 2002;Pearce et al, 2013b) and leads to increasing concentrations of lipopolysaccharide (LPS) in portal and systemic blood (Hall et al, 2001). Further, endotoxemia is common among heat stroke patients (Leon, 2007) and it is thought to play a central role in heat stroke pathophysiology, as survival increases when intestinal bacterial load is reduced (Bynum et al, 1979) or when plasma LPS is neutralized (Gathiram et al, 1987).…”

Overcrowding stress decreases macrophage activity and increasesSalmonellaEnteritidis invasion in broiler chickens

“…Numerous authors have reported that environmental stressors affect intestinal barrier integrity, which is composed of enterocytes, tight junctions, secreted mucous and immune cells, such as macrophages (Lambert et al, 2002;Prosser et al, 2004;Singleton & Wischmeyer, 2006;Chappell et al, 2009;Lambert, 2009).…”

Neurohumoral responses during prolonged exercise in humans

“…Thus dopamine in the sympathetic ganglia is secreted mainly from the sensory neurons (3). Finally, dopamine may originate from food in the gastrointestinal tract (18), and its appearance in the blood could increase, because the permeability of the gastrointestinal barrier may increase during hyperthermia (35).…”