L-arginine attenuates trauma-hemorrhage-induced liver injury.
OBJECTIVE
Liver injury is common after trauma-hemorrhage for which the underlying mechanism is not clear. Although administration of the essential amino acid L-arginine has been reported to restore the depressed cardiovascular functions and cell-mediated immune responses after trauma-hemorrhage, it remains unknown whether L-arginine protects against liver injury under those conditions.


METHODS
A prospective, controlled animal study.


METHODS
A university research laboratory.


METHODS
Male Sprague-Dawley rats.


METHODS
Rats underwent sham operation or laparotomy and were bled to and maintained at a mean arterial blood pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of lactated Ringer's solution. Hemorrhaged rats were then resuscitated with lactated Ringer's solution, four times the maximum shed blood volume over 1 hr. During resuscitation, animals received either 300 mg/kg of L-arginine or saline (vehicle) intravenously. At 3 and 5 hrs after resuscitation, rats were killed, blood was obtained, and the liver was fixed for histology (hematoxylin & eosin staining). Plasma glutathione S-transferase (a marker of liver damage), L-arginine, citrulline, and ornithine concentrations were assessed.


RESULTS
The increased concentrations of plasma glutathione S-transferase observed in vehicle-treated hemorrhage animals were normalized with L-arginine treatment at 5 hrs after resuscitation. Moreover, the histology indicated that L-arginine prevented liver edema and neutrophil infiltration after trauma-hemorrhage. Plasma L-arginine and citrulline were increased in L-arginine-treated rats.


CONCLUSIONS
Because citrulline is a by-product of nitric oxide generation by nitric oxide synthase from L-arginine, this amino acid may be a useful adjunct for preventing hepatic injury after trauma-hemorrhage via endothelial derived nitric oxide production.
Angele
M K
MK
Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence, USA.
Fitzal
F
F
Smail
N
N
Knöferl
M W
MW
Schwacha
M G
MG
Ayala
A
A
Wang
P
P
Chaudry
I H
IH
D000818:Animals; D001120:Arginine / Q000097:blood / Q000494:pharmacology*; D002956:Citrulline / Q000097:blood; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D005982:Glutathione Transferase / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006470:Hemorrhage / Q000473:pathology / Q000503:physiopathology*; D007111:Immunity, Cellular / Q000187:drug effects* / Q000502:physiology; D008099:Liver / Q000293:injuries* / Q000473:pathology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D009952:Ornithine / Q000097:blood; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation
D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D009952:Ornithine; D005982:Glutathione Transferase