L-arginine attenuates trauma-hemorrhage-induced liver injury

Objectives: Liver injury is common after trauma-hemorrhage for which the un derlying mechanism is not clear, Although administration of the essential a mino acid L-arginine has been reported to restore the depressed cardiovascu lar functions and cell-mediated immune responses after trauma-hemorrhage, i t remains unknown whether L-arginine protects against liver injury under th ose conditions, Design:A prospective, controlled animal study. Setting: A university research laboratory. Subjects: Male Sprague-Dawley rats. Interventions: 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 s olution, four times the maximum shed blood volume over 1 hr, During resusci tation, 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 s taining), Plasma glutathione S-transferase (a marker of liver damage), L-ar ginine, citrulline, and ornithine concentrations were assessed, Measurements and Main Results: The increased concentrations of plasma gluta thione S-transferase observed in vehicle-treated hemorrhage animals were no rmalized with L-arginine treatment at 5 hrs after resuscitation. Moreover, the histology indicated that L-arginine prevented liver edema and neutrophi l infiltration after trauma-hemorrhage. Plasma L-arginine and citrulline we re increased in L-arginine-treated rats, Conclusions:Because citrulline is a by-product of nitric oxide generation b y nitric oxide synthase from L-arginine, this amino acid may be a useful ad junct for preventing hepatic injury after trauma-hemorrhage via endothelial derived nitric oxide production.