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

Lambert, G. P., C. V. Gisolfi,† D. J. Berg, P. L. Moseley, L. W. Oberley, and K. C. Kregel. Selected Contribution: Hyperthermia-induced intestinal permeability and the role of oxidative and nitrosative stress. J Appl Physiol 92: 1750–1761, 2002. First published November 2, 2001; 10.1152/japplphysiol.00787.2001.—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 37°C or heated over 90 min to a core body temperature of 41, 41.5, or 42.5°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