Skeletal Muscle PGF_2αand PGE₂in Response to Eccentric Resistance Exercise: Influence of Ibuprofen and Acetaminophen

Abstract

PGs have been shown to modulate skeletal muscle protein metabolism as well as inflammation and pain. In nonskeletal muscle tissues, the over the counter analgesic drugs ibuprofen and acetaminophen function through suppression of PG synthesis. We previously reported that ibuprofen and acetaminophen inhibit the normal increase in skeletal muscle protein synthesis after high intensity eccentric resistance exercise. The current study examined skeletal muscle PG levels in the same subjects to further investigate the mechanisms of action of these drugs in exercised skeletal muscle. Twenty-four males (25 +/- 3 yr) were assigned to 3 groups that received the maximal over the counter dose of ibuprofen (1200 mg/d), acetaminophen (4000 mg/d), or a placebo after 10-14 sets of 10 eccentric repetitions at 120% of concentric 1 repetition maximum using the knee extensors. Preexercise and 24 h postexercise biopsies of the vastus lateralis revealed that the exercise-induced change in PGF(2alpha) in the placebo group (77%) was significantly different (P < 0.05) from those in the ibuprofen (-1%) and acetaminophen (-14%) groups. However, the exercise-induced change in PGE(2) in the placebo group (64%) was only significantly different (P < 0.05) from that in the acetaminophen group (-16%). The exercise-induced changes in PGF(2alpha) and PGE(2) were not different between the ibuprofen and acetaminophen groups. These results suggest that ibuprofen and acetaminophen have a comparable effect on suppressing the normal increase in PGF(2alpha) in human skeletal muscle after eccentric resistance exercise, which may profoundly influence the anabolic response of muscle to this form of exercise.

Impact of acetaminophen consumption and resistance exercise on extracellular matrix gene expression in human skeletal muscle

“…Similarly, Tsai et al noted that 72 h of IBU treatment does not affect mRNA or protein expression of COL1A1 and COL3A1 in cell culture (26). Given that APAP has been shown to share peripheral targets with nonsteroidal anti-inflammatory drugs like IBU (14,23), these cell culture findings are consistent with our findings where collagen mRNA expression was unchanged with analgesics. Surprisingly, we also did not observe an increase in collagen mRNA expression with acute RE even though others have noted a robust increase in skeletal muscle collagen synthesis with acute exercise (19).…”

“…It is commonly thought that APAP produces its analgesic effect via the central nervous system. Despite this, APAP has displayed an ability to inhibit, in peripheral tissues, cyclooxygenase (COX), an upstream enzyme responsible for the production of products known to modulate pain and inflammation (14,23). Several studies have also provided convincing evidence that APAP alters cellular signaling and exercise-induced adaptions in skeletal muscle and tendon (4 -6, 11, 22, 30 -32), including reducing skeletal muscle collagen and cross-linking content (6).…”

Prostaglandin synthesis can be inhibited locally by infusion of NSAIDS through microdialysis catheters in human skeletal muscle

“…graded blockade; prostaglandin E2; inflammation; eccentric exercise PROSTAGLANDINS (PGS) ARE KNOWN TO be involved in the regulation of local blood flow within human skeletal muscles during exercise (1,16), and the concentrations of circulating proinflammatory cytokines (12) and PGs (17) are found to increase locally as well as systemically in response to exercise. PGs are synthesized from arachidonic acid derived from cell membrane phospholipids by cyclooxygenase (COX) enzymes, and the systemic release of PGs can be inhibited by oral administration of COX inhibitors known as nonsteroidal anti-inflammatory drugs (NSAIDs).…”

A prostaglandin alpha F2 analog protects from statin-induced myopathic changes in primary human muscle cells

“…In our study, treatment with PGF2a did not significantly change myoblast proliferation and differentiation under statin treatment but PGF2a secretion initially increased under simvastatin treatment together with PGD2, another proinflammatory PG. In a clinical study, eccentric resistance exercise initially revealed high PGF2a levels in human skeletal muscle biopsy specimens 44 . PGD2 metabolites are also linked to DMD suggesting a role in muscle cell pathology 45 .…”