Ibuprofen effects on the response to exertional heat stroke in male and female mice
Authors: Garcia Christian Kyle , Sheikh Laila H , Iwaniec John D , Robinson Gerard P , Berlet Reed A , Mattingly Alex , Laitano Orlando , Murray Kevin , Clanton Thomas 
Published: June 2021

One of the major risks of exertional heat stroke (EHS) is increased intestinal damage. Further intestinal damage may be exacerbated while using non‐steroidal anti‐inflammatory drugs (NSAIDs) in the heat. Ibuprofen (IBU) is the most commonly used NSAID in the United States. It is an inhibitor of both COX‐1 and COX‐2, decreasing prostaglandins involved in the maintenance of the intestinal lining, induction of fever, and platelet aggregation. Using a preclinical model of EHS, we investigated the effects of ibuprofen on performance and intestinal damage in a hyperthermic environment.PURPOSETo investigate the effects of high dose ibuprofen on intestinal damage and determine if an effect exist in both sexes using a preclinical EHS model.METHODSForty‐two mice were separated by sex and into either a placebo (PLA) group or an IBU fed group. Animals were implanted with a telemetry device for detecting core temperature (Tc). Wheels were placed inside the mouse cages for 3 weeks of ad libitum training as well as four days of training on a forced running wheel. The IBU was delivered as an additive within the same dietary feed over 48 h prior to EHS. Mice were placed in the forced running wheel within an environmental chamber heated to 37.5°C. They first underwent an incremental phase (IP) of exercise and once Tc reached 41°C they entered a steady‐state phase (SP). Endpoint was determined by loss of consciousness. Once mice had completed the EHS protocol, plasma and tissue samples were collected at 3 hours. An ELISA for fatty acid binding protein 2 (FABP2), a biomarker of intestinal damage, was used between groups. We used an ANCOVA to account for the effects of sex, body surface area/mass (BSA/m), and treatment.RESULTSTime to core temperature maximum was higher in females than in males and was attributed to differences in sex (p=0.0003). Significant differences from baseline temperature to 39.5°C were associated with both sex and BSA/m (p=0.0004). Females had longer times in the heat from 39.5°C – 41°C (p=0.0013). IBU had a significantly prolonged the length of SP in both sexes (p=0.0417). Maximum core temperature (Tc, max) was significantly greater in those treated with IBU (p=0.0010), regardless of sex. Ascending thermal area, max speed, and maximum distance run were greater in females regardless of treatment (p=0.0002, p=0.0017, and p=0.0006). FABP2 was significantly greater in the IBU group with heat when compared to exercise controls in both males and females (p=0.03 and p=0.01) but it was not significantly greater than EHS alone. FABP2 was also significantly greater in females than males within the IBU groups with heat (p=0.005). Our data suggest that IBU influenced thermoregulation but had only minor influences on intestinal injury in this model.Support or Funding InformationSupported by DOD Grant W81XWH‐15‐2‐0038. Author's views not official US Army or DoD policyThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.