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Department of Anesthesiology and Intensive Care, Clinical Research Center, Huddinge University Hospital; Department of Surgery, St. Görans Hospital; and Karolinska Institute, 141 86 Huddinge, Stockholm, Sweden
To gain insight into cellular metabolism
underlying the glutathione (GSH) alterations induced by surgical
trauma, we assessed postoperative skeletal muscle GSH metabolism and
its redox status in 10 patients undergoing elective abdominal surgery.
Muscle biopsy specimens were taken from the quadriceps femoris muscle
before and at 24 and 72 h after surgery. GSH concentrations decreased by 40% at 24 h postoperatively compared with the paired preoperative values (P < 0.001) and remained low
at 72 h (P < 0.01). The
concentration of GSH disulfide (GSSG) did not significantly change
throughout the study period, whereas the total GSH (as GSH equivalent)
concentration decreased after surgery. Of the GSH constituent amino
acids, the concentration of cysteine remained unchanged throughout the
study period (from 28.2 ± 10.1 preoperatively to 29.4 ± 13.9 at 24 h postoperatively and to 28.3 ± 15.6 µmol/kg wet
wt at 72 h postoperatively). Despite a reduction in glutamate
concentration by 40% 24 h after surgery, no correlation was
established between GSH and glutamate concentrations postoperatively.
Activity of
-glutamylcysteine synthetase did not change
significantly after surgery, whereas GSH synthetase activity decreased
postoperatively (from 66.4 ± 19.1 preoperatively to 41.0 ± 10.5 24 h postoperatively, P < 0.01, and
to 46.0 ± 11.7 µU/mg protein 72 h postoperatively,
P < 0.05). The decrease of GSH was
correlated to the reduced GSH synthetase activity seen at 24 h
postoperatively. These results indicate that the skeletal muscle GSH
pool is diminished in patients after surgical trauma. The depletion of
the GSH pool is associated with a decreased activity of GSH synthetase,
indicating a decreased GSH synthetic capacity in skeletal muscle
tissue.
glutathione synthetase
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