Arginine deficiency in bile duct-ligated rats after surgery: the role of plasma arginase and gut endotoxin restriction.
OBJECTIVE
Arginine deficiency may underlie the cellular immune depression after surgery in obstructive jaundice, which is associated with gut-derived endotoxemia. The aim of this study was to study arginine metabolism in the bile duct-ligated rat (BDL) after laparotomy.


METHODS
Treatment with cholestyramine, a known endotoxin binder, was used to evaluate the role of gut-derived endotoxemia.


RESULTS
In BDL rats, arginine levels were lower compared with those in sham-operated controls (P < 0.005), despite a three-fold increase in renal arginine release (P < 0.01). Liver and gut arginine handling also could not explain the reduced arginine levels. Higher plasma arginase activity (P < 0.0001) was measured in BDL rats, explaining both the lower arginine levels (r = 0.73, P < 0.01) and the increase in arginase product levels: ornithine (P < 0.005 and r = 0.72; P < 0.01) and urea (P < 0.01). Cholestyramine treatment prevented the decrease in postoperative arginine deficiency by reducing plasma arginase activity by 43% (P < 0.005). In addition, it significantly lowered plasma levels of the other liver enzymes (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, and alkaline phosphatase; P < 0.05) in BDL rats.


CONCLUSIONS
The study concluded that arginine deficiency in BDL rats after surgery is caused by high plasma liver arginase activity. Cholestyramine prevented the arginine deficiency by reducing plasma arginase activity through the inhibition of additional endotoxin-mediated hepatocellular damage after surgery in BDL rats.
Houdijk
A P
AP
Department of Surgery, Free University Hospital, Amsterdam, The Netherlands.
Teerlink
T
T
Visser
J J
JJ
van Lambalgen
A A
AA
van Leeuwen
P A
PA
D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors / Q000097:blood*; D001120:Arginine / Q000172:deficiency* / Q000378:metabolism; D002779:Cholestasis / Q000097:blood / Q000150:complications*; D002792:Cholestyramine Resin / Q000494:pharmacology*; D003135:Common Bile Duct / Q000502:physiology / Q000601:surgery*; D019446:Endotoxemia / Q000209:etiology / Q000517:prevention & control*; D006400:Hematocrit; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009952:Ornithine / Q000378:metabolism; D011183:Postoperative Complications; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D014508:Urea / Q000378:metabolism
D009566:Nitrates; D009573:Nitrites; D002792:Cholestyramine Resin; D014508:Urea; D001120:Arginine; D009952:Ornithine; D001119:Arginase