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  • Title: Effect of cyclooxygenase-2 inhibition by meloxicam, on atrogin-1 and myogenic regulatory factors in skeletal muscle of rats injected with endotoxin.
    Author: Martin AI, Nieto-Bona MP, Castillero E, Fernandez-Galaz C, Lopez-Menduina M, Gomez-Sanmiguel AB, Gomez-Moreira C, Villanua MA, Lopez-Calderon A.
    Journal: J Physiol Pharmacol; 2012 Dec; 63(6):649-59. PubMed ID: 23388481.
    Abstract:
    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.
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