Negative interaction between indomethacin and exercise in mice

We examined the possible negative interaction of the combined use of the NSAID indomethacin (IND) and exercise in mice. Mice were assigned to one of 4 groups: Exercise 2.5 mg/kg IND (Ex-2.5), Sedentary 2.5 mg/kg IND (Sed-2.5), Exercise 5.0 mg/kg IND (Ex-5.0) and Sedentary 5.0 mg/kg IND (Sed-5.0). Mice were given IND (gavage) 1 h prior to exercise (treadmill run at 30 m/min, 8% grade for 90 min) or rest for 14 consecutive days. Run times, body weight and mortality were recorded daily. Sed-5.0 was highly toxic and caused 70% mortality compared to Sed-2.5, which was well tolerated (0% mortality) (P<0.05). While the addition of exercise had no greater effect on mortality in Ex-5.0, it increased it in the 2.5 group (52% vs. 0%; P<0.05). Run time was reduced from baseline beginning on day 2 (Ex-5.0), or day 3 (Ex-2.5) (P<0.05). Body weight (recorded in the 2.5 mg/kg groups only) was decreased from baseline in Ex-2.5 and Sed-2.5 (P<0.05), but this effect occurred earlier and was of greater magnitude in Ex-2.5. Exercise combined with IND use can lead to serious side effects in mice. Future research is needed to test the hypothesis that this effect is due to increased GI permeability and whether humans are also at risk.