title: The effect of chronic treadmill exercise and acetaminophen on collagen and cross-linking in rat skeletal muscle and heart.
abstract: The purpose of this study was to determine whether exercise and/or acetaminophen (APAP) alter collagen and cross-linking in the rat gastrocnemius muscle, soleus muscle, and heart. Male Wistar rats (n = 50; 8 wk old) were divided into placebo (PLA) or APAP groups and sedentary (SED) or exercised (RUN) groups. APAP (200 mg/kg) was administered daily by oral gavage. Exercised groups ran on a treadmill 5 days/wk for 8 wk with progression to 60 min/day, 20 m/min, and 8° incline. Tissues were assayed for collagen (hydroxyproline) and hydroxylyslpyridinoline (HP) and lysylpyridinoline (LP) cross-links by HPLC. Collagen content (μg/mg dry weight) was greater in both the gastrocnemius (SED-PLA: 114 ± 16 vs.
  244 ± 32; P < 0.001) and soleus (SED-PLA: 51 ± 7 vs.
  99 ± 27; P = 0.005) of exercised animals. In contrast, collagen content was not significantly greater in exercised animals treated with APAP (SED-APAP: 113 ± 16 vs.
  145 ± 21) and soleus (SED-APAP: 55 ± 8 vs.
  57 ± 10). HP cross-linking (mmol/mol collagen) in the gastrocnemius (SED-PLA: 126 ± 28, RUN-PLA: 50 ± 7, SED-APAP: 41 ± 7, and
  30 ± 4) and soleus muscles (SED-PLA: 547 ± 107, RUN-PLA: 318 ± 92, SED-APAP: 247 ± 64, and
  120 ± 17) was lower in exercised rats compared with sedentary rats (P < 0.05). Cross-linking was further reduced in animals treated with APAP (P < 0.05). Neither heart collagen nor cross-linking was influenced by exercise or APAP (P > 0.05). Our findings suggest that exercise and APAP have tissue-specific effects on muscle collagen. Given the widespread use of APAP as an analgesic and antipyretic, further work in humans is warranted.
authors.affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Arizona ccarro@midwestern.edu.
authors.forename: Chad C
authors.initials: CC
authors.lastname: Carroll
authors.affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Arizona.
authors.forename: Karl
authors.initials: K
authors.lastname: Martineau
authors.affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Arizona.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Arthur
authors.affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Arizona.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Huynh
authors.affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Arizona.
authors.forename: Brent D
authors.initials: BD
authors.lastname: Volper
authors.affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Arizona.
authors.forename: Tom L
authors.initials: TL
authors.lastname: Broderick
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D058633:Antipyretics / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism*; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D005082:Physical Exertion; D017208:Rats, Wistar; D012420:Running; D057185:Sedentary Behavior; D013997:Time Factors
chemical_list: D000596:Amino Acids; D000700:Analgesics; D058633:Antipyretics; D000082:Acetaminophen; C015484:pyridinoline; C036020:deoxypyridinoline; D003094:Collagen; D006909:Hydroxyproline
keywords: acetaminophen; collagen; exercise; rat; skeletal muscle