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

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.