Aspirin as a COX inhibitor and anti-inflammatory drug in human skeletal muscle

Abstract

Although aspirin is one of the most common anti-inflammatory drugs in the world, the effect of aspirin on human skeletal muscle inflammation is almost completely unknown. This study examined the potential effects and related time course of an orally consumed aspirin dose on the inflammatory prostaglandin E (PGE)/cyclooxygenase (COX) pathway in human skeletal muscle. Skeletal muscle biopsies were taken from the vastus lateralis of 10 healthy adults (5 male and 5 female, 25 ± 2 yr old) before (Pre) and 2, 4, and 24 h after (Post) a standard dose (975mg) of aspirin and partitioned for analysis of 1) in vivo PGE levels in resting skeletal muscle and 2) ex vivo skeletal muscle PGE production when stimulated with the COX substrate arachidonic acid (5 μM). PGE levels in vivo and PGE production ex vivo were generally unchanged at each time point after aspirin consumption. However, most individuals clearly showed suppression of PGE, but at varying time points after aspirin consumption. When the maximum suppression after aspirin consumption was examined for each individual, independent of time, PGE levels in vivo (184 ± 17 and 104 ± 23pg/g wet wt at Pre and Post, respectively) and PGE production ex vivo (2.74 ± 0.17 and 2.09 ± 0.11pg·mg wet wt·min at Pre and Post, respectively) were reduced ( P < 0.05) by 44% and 24%, respectively. These results provide evidence that orally consumed aspirin can inhibit the COX pathway and reduce the inflammatory mediator PGE in human skeletal muscle. Findings from this study highlight the need to expand our knowledge regarding the potential role for aspirin regulation of the deleterious influence of inflammation on skeletal muscle health in aging and exercising individuals. NEW & NOTEWORTHY This study demonstrated that orally consumed aspirin can target the prostaglandin/cyclooxygenase pathway in human skeletal muscle. This pathway has been shown to regulate skeletal muscle metabolism and inflammation in aging and exercising individuals. Given the prevalence of aspirin consumption, these findings may have implications for skeletal muscle health in a large segment of the population.

Resistance Training with Co-ingestion of Anti-inflammatory Drugs Attenuates Mitochondrial Function

“…In a comparison between 1,500 and 100 mg aspirin, it was concluded that low-dose ASA can effectively inhibit platelet function without producing pharmacologically active concentrations in the peripheral circulation (Rosenkranz and Frölich, 1985 ). The dose in the current study (75 mg) is also more than 10 times lower than used in the recent study by Ratchford et al where muscle prostaglandin levels were unchanged or only modestly suppressed by 975 mg aspirin (Ratchford et al, 2017 ).…”

Ameliorative role of aspirin in paraquat‐induced lung toxicity via mitochondrial mechanisms

“…This feature prevents ATP generation . ASA inhibits cyclooxygenase, which can remove hydroxy radical's production due to antioxidant and anti‐inflammatory properties of ASA . It also reduces the oxidative stress and inhibits NF‐κB by inhibiting TNF‐α .…”

Influence of low‐dose aspirin, resistance exercise, and sex on human skeletal muscle PGE2/COX pathway activity

“…Aspirin is a potent cyclooxygenase (COX) inhibitor that is commonly consumed for its anti‐inflammatory and cardioprotective effects (O'Brien et al, 2019; Stuntz & Bernstein, 2017; Zhou et al, 2014). Recent investigations have shown that aspirin inhibits COX production of the inflammatory regulator prostaglandin E 2 (PGE 2 ) in resting human skeletal muscle under in vivo and ex vivo conditions (Fountain et al, 2020; Ratchford et al, 2017). Considering that aspirin is consumed chronically at low doses by an estimated 65 million adults in the United States, it is noteworthy that low‐dose aspirin significantly reduces skeletal muscle PGE 2 production (Fountain et al, 2020).…”

“…In particular, PGE 2 , the most abundant PG produced in skeletal muscle, regulates skeletal muscle protein metabolism and inflammation through its autocrine and paracrine influence on myocellular and molecular processes, ultimately impacting skeletal muscle mass and function (Ho et al, 2017; Korotkova & Lundberg, 2014; Liu et al, 2016; Schaap et al, 2009; Standley et al, 2013; Trappe & Liu, 2013; Trappe et al, 2013). In addition, resistance exercise results in unique alterations in the intracellular environment (Adams & Bamman, 2012; Egan & Zierath, 2012; Powers et al, 2016), which may influence COX enzyme function or the efficacy of drugs that inhibit COX (Feldman et al, 2000; Liu et al, 2016; Ratchford et al, 2017; Simmons et al, 2004; Smith & Malkowski, 2019; Smith et al, 2011; Trappe & Liu, 2013). Yet, the potential influence of aspirin on skeletal muscle PGE 2 /COX pathway activity after resistance exercise is unknown.…”

“…Specifically, absorption and clearance appear to be influenced, but these studies do not provide skeletal muscle‐specific information. As there are few investigations into the effects of aspirin on skeletal muscle (Fountain et al, 2020; Ratchford et al, 2017), any potential sex‐specific effects are unknown. Lack of sex‐specific information is not uncommon in drug development, and there are likely more differences in drug responsiveness between men and women than has been previously appreciated (Zucker & Prendergast, 2020).…”