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

• Published in: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society Vol. 63; no. 6; p. 649
• Main Authors: Martin, A I, Nieto-Bona, M P, Castillero, E, Fernandez-Galaz, C, Lopez-Menduina, M, Gomez-Sanmiguel, A B, Gomez-Moreira, C, Villanua, M Angeles, Lopez-Calderon, A
• Format: Journal Article
• Language: English
• Published: Poland 01.12.2012
• Subjects: Animals; Blotting, Western; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; Injections, Intraperitoneal; Lipopolysaccharides - administration & dosage; Male; 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; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; RNA, Messenger - metabolism; 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
• ISSN: 1899-1505

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.