Ibuprofen Effects on the Response to Exertional Heat Stroke in Male and Female Mice

ABSTRACT Intestinal injury is one of the most prominent features of organ damage in exertional heat stroke (EHS). However, whether damage to the intestine in this setting is exacerbated by ibuprofen (IBU), the most commonly used nonsteroidal anti-inflammatory drug in exercising populations, is not well understood. Purpose We hypothesized that IBU would exacerbate intestinal injury, reduce exercise performance, and increase susceptibility to heat stroke. Methods To test this hypothesis, we administered IBU via diet to male and female C57/BL6J mice, over 48 h before EHS. Susceptibility to EHS was determined by assessing exercise response using a forced running wheel, housed inside an environmental chamber at 37.5°C. Core temperature (Tc) was monitored by telemetry. Mice were allocated into four groups: exercise only (EXC); EHS + IBU; EXC + IBU; and EHS only. Exercise performance and Tc profiles were evaluated and stomachs, intestines and plasma were collected at 3 h post-EHS. Results The EHS + IBU males ran approximately 87% longer when Tc was above 41°C (P < 0.03) and attained significantly higher peak Tc (P < 0.01) than EHS-only mice. Histological analyses showed decreased villi surface area throughout the small intestine for both sexes in the EXC + IBU group versus EXC only. Interestingly, though EHS in both sexes caused intestinal injury, in neither sex were there any additional effects of IBU. Conclusions Our results suggest that in a preclinical mouse model of EHS, oral IBU at pharmacologically effective doses does not pose additional risks of heat stroke, does not reduce exercise performance, and does not contribute further to intestinal injury, though this could have been masked by significant gut injury induced by EHS alone.