Effect of cyclooxygenase-2 inhibition by meloxicam, on atrogin-1 and myogenic regulatory factors in skeletal muscle of rats injected with endotoxin

J Physiol Pharmacol. 2012 Dec;63(6):649-59.


Cyclooxygenase-2-induction by inflammatory stimuli has been proposed as a mediator of inflammatory cachexia. We analyse whether cyclooxygenase-2 inhibition by meloxicam administration is able to modify the response of skeletal muscle to inflammation induced by lipopolysaccharide endotoxin (LPS). Male rats were injected with 1 mg kg(-1) LPS at 17:00 h and at 10:00 h the following day, and euthanized 4, 24 or 72 hours later. Atrogin-1, MuRF1, myogenic regulatory factors and cyclooxygenase-2 in the gastrocnemius were determined by real time-PCR (mRNA) and Western blot (protein). In a second experiment the effect of meloxicam administration (1 mg kg⁻¹) was analyzed. Meloxicam was administered either in a preventive manner, 1 hour before each endotoxin injection, or in a therapeutic manner, starting 2 hours after the second LPS injection and at 24 and 48 hours afterwards. There was a marked increase in MuRF1 mRNA (P<0.01) 4 hours after LPS, and in atrogin-1 mRNA 4 hours (P<0.01) and 24 hours (P<0.01) after LPS. Cyclooxygenase-2 was increased, whereas MyoD was decreased at 4, 24 and 72 h. Both types of meloxicam treatment blocked LPS-induced increase in atrogin-1. Preventive, but not therapeutic, meloxicam decreased myostatin (P<0.01) and increased Pax7 (P<0.01) and MyoD (P<0.05). Therapeutic meloxicam treatment decreased gastrocnemius myogenin. These data suggest that cyclooxygenase-2 inhibition by meloxicam administration can prevent the increase in atrogin-1 and the decrease in MyoD induced by LPS administration. However, prolonged therapeutic meloxicam treatment seems to be less effective, since it can inhibit myogenic regulatory factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Injections, Intraperitoneal
  • Lipopolysaccharides / administration & dosage*
  • Male
  • Meloxicam
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • MyoD Protein / genetics
  • MyoD Protein / metabolism
  • Myogenic Regulatory Factors / genetics
  • Myogenic Regulatory Factors / metabolism*
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • SKP Cullin F-Box Protein Ligases / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism*
  • Thiazines / pharmacology*
  • Thiazoles / pharmacology*
  • Time Factors
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism


  • Cyclooxygenase 2 Inhibitors
  • Lipopolysaccharides
  • Muscle Proteins
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Myogenic Regulatory Factors
  • PAX7 protein, rat
  • Paired Box Transcription Factors
  • RNA, Messenger
  • Thiazines
  • Thiazoles
  • Tripartite Motif Proteins
  • lipopolysaccharide, E coli O55-B5
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Fbxo32 protein, rat
  • SKP Cullin F-Box Protein Ligases
  • Trim63 protein, rat
  • Ubiquitin-Protein Ligases
  • Meloxicam