Influence of acetaminophen consumption and exercise on Achilles tendon structural properties in male Wistar rats

Carroll CC, Whitt JA, Peterson A, Gump BS, Tedeschi J, Broderick TL. Influence of acetaminophen consumption and exercise on Achilles tendon structural properties in male Wistar rats. Am J Physiol Regul Integr Comp Physiol 302: R990-R995, 2012. First published February 22, 2012; doi: 10.1152/ajpregu.00659.2011.-Chronic consumption of acetaminophen (APAP) during exercise training leads to a reduction in tendon stiffness and modulus compared with a placebo. We explored whether this effect could be due to a reduction in tendon collagen content or cross-linking. Ten-week-old male Wistar rats (n = 50) were divided into placebo or APAP groups and into sedentary or treadmill-exercised groups. APAP (200 mg/kg) or saline was administered once daily by oral gavage. Rats in the exercise groups ran on a treadmill 5 days per week for 8 wk with progression to 60 min per day, 20 m/min, and 8 degrees incline. After 8 wk, lyophilized Achilles tendon samples were assayed for the collagen-specific amino acid hydroxyproline and cross-linking [hydroxylyslpyridinoline (HP)] content by high-performance liquid chromatrography. Collagen content was not influenced by exercise or APAP (P > 0.05). Compared with placebo, tendon water content was 7% (P = 0.006, main effect) lower in animals consuming APAP (placebo: 54.79 +/- 0.8%, APAP: 50.89 +/- 1.2%). HP in the Achilles tendon was 36% greater (sedentary: 141 +/- 15, exercise: 204 +/- 26 mmol/mol collagen) in the exercise-trained rats independent of drug treatment (P = 0.020, main effect). Independent of exercise, HP content was 33% lower (P = 0.032, main effect) in the animals consuming APAP (placebo: 195 +/- 21, APAP: 140 +/- 19 mmol/mol collagen). Our data suggests that chronic consumption of APAP results in a reduction in collagen cross-linking and a loss of tissue water independent of chronic exercise. This reduction in cross-linking and water content could contribute to the decrease in tendon stiffness noted in humans chronically consuming APAP.