The effect of indomethacin on muscle and liver protein synthesis and on whole-body protein degradation during abdominal sepsis in the rat.
It has been recently suggested that increased muscle protein degradation during injury or infection is at least partially mediated by the increased production of prostaglandin E2 in muscle, and some have suggested that cyclooxygenase inhibitors might decrease protein loss in injured or septic patients. In these experiments, fractional synthesis rates of mixed muscle and liver protein and whole-body tyrosine flux were measured by constant intravenous infusion of tyrosine labeled with carbon 14 in 17 rats with sham operations and 15 severely septic rats with or without indomethacin treatment (20 mg/kg/d). Fractional synthesis rates in muscle and liver were decreased in late sepsis and were lowest in the septic group receiving indomethacin. Unlike the fractional synthesis rate, which was affected by indomethacin in septic rats only, tyrosine flux was significantly lower in indomethacin-treated rats with sham operations and those with sepsis. Although indomethacin reduced total-body protein breakdown during sepsis, it was also associated with lower plasma albumin levels and with decreased protein synthesis in muscle and liver at a time when the survival of the septic host may be dependent on its ability to produce new protein for a variety of vital functions. These results do not support the use of indomethacin in sepsis.
Freund
H R
HR
James
J H
JH
LaFrance
R
R
Gallon
L S
LS
Barcelli
U O
UO
Edwards
L L
LL
Joffe
S N
SN
Bjornson
H S
HS
Fischer
J E
JE
D000005:Abdomen; D000596:Amino Acids / Q000097:blood; D000818:Animals; D002250:Carbon Radioisotopes; D015232:Dinoprostone; D007213:Indomethacin / Q000494:pharmacology*; D007239:Infections / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014443:Tyrosine / Q000378:metabolism
D000596:Amino Acids; D002250:Carbon Radioisotopes; D011458:Prostaglandins E; D011506:Proteins; D014443:Tyrosine; D015232:Dinoprostone; D007213:Indomethacin