Nsaids Do Not Affect Muscle Signaling In Exercising Rats

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin synthesis produced by the cyclooxygenase (COX) enzymes, which regulate physiological processes including muscle protein signaling. Previous research has shown that NSAIDs interfere with muscle protein synthesis and metabolism pathways in response to acute exercise, while chronic exercise studies show equivocal results although more than two NSAIDs have never been tested in a single study. Therefore, our goal was to determine the effects of four NSAIDs, ranging in COX affinity, in rats after six weeks of exercise. We hypothesized that NSAIDs would inhibit muscle growth and metabolism pathways. METHODS: 9-week-old male Wistar rats (n = 100) were randomized and treated daily with either placebo (PLA) a low dose of naproxen (NAP), Acetaminophen (ACT), ibuprofen (IBU), or flurbiprofen (FLU) with or without exercise (EX). Rats were exercised for 30 mins per day on a treadmill at 15 m/min with a 5% incline, 5 days per week, for six weeks. Quadricep muscle was harvested 45-60 mins post-exercise at the end of the six weeks. Immunoblotting was performed for phosphorylated and total protein levels of AKT Ser473, S6 Ser235/236, S6 Ser240/244, AMPKα Thr172 and 4EBP1 Ser65. Fold changes were calculated from PLA. Data were analyzed using a two-way ANOVA and are presented as mean ± SD. RESULTS: There were no significant differences compared to PLA for: p-AKT Ser473/Total AKT, p-S6 Ser235/236/Total S6, p-S6 Ser240/244/Total S6, p-AMPKα Thr172/Total AMPK or p-4EBP1/4EBP1 (all, p > 0.05). CONCLUSION: Contrary to our hypothesis, muscle growth and metabolism pathways were not influenced by exercise or chronic low doses of NSAIDs. This data suggests that higher doses of NSAIDs or more intense exercise may be required to influence these pathways. The views expressed in this abstract are those of the authors and do not reflect the official policy of the Department of Army, Department of Defense, or the U.S. Government. - p-AKT Ser473/Total AKT p-S6 Ser235/Total S6 p-S6 Ser240/Total S6 p-4EBP1 S65 /4EBP1 p-AMPKα Thr172/Total AMPK PLA + EX 1.49 ± 0.72 1.11 ± 1.07 1.45 ± 1.50 0.43 ± 0.25 1.82 ± 0.90 NAP 1.02 ± 0.64 0.83 ± 0.57 0.77 ± 0.38 1.10 ± 0.63 1.40 ± 1.08 NAP + EX 1.23 ± 0.69 2.62 ± 2.80 1.67 ± 1.86 0.58 ± 0.57 1.02 ± 0.42 ACET 1.14 ± 0.42 0.93 ± 0.51 1.02 ± 0.39 1.19 ± 0.54 0.88 ± 0.38 ACET + EX 1.11 ± 0.58 0.86 ± 0.63 0.83 ± 0.33 0.92 ± 0.63 1.00 ± 0.51 IBU 0.93 ± 0.47 1.16 ± 0.82 1.18 ± 1.02 0.69 ± 0.23 0.98 ± 0.48 IBU + EX 1.01 ± 0.36 1.93 ± 1.78 1.26 ± 0.82 0.73 ± 0.50 2.20 ± 0.94 FLU 0.99 ± 0.71 0.92 ± 0.49 1.21 ± 0.69 0.91 ± 0.36 1.40 ± 1.44 FLU + EX 0.96 ± 0.55 2.19 ± 2.51 1.50 ± 1.49 1.08 ± 0.72 1.46 ± 0.73