Critical role of oxygen radicals in the initiation of hepatic depression after trauma hemorrhage

Background: Although depression in hepatocellular function occurs early aft er trauma and severe hemorrhage and persists despite fluid resuscitation, i t remains unknown whether reactive oxygen species (ROS) play any role in th e initiation of hepatocellular depression and damage under those conditions . We hypothesized that administration of a ROS scavenger at the beginning o f resuscitation will attenuate organ injury after severe shock. Methods: Male Sprague-Dawley rats (275-325 g) underwent laparotomy (i,e,, i nduction of soft tissue trauma) and were then bled to and maintained at a m ean arterial pressure of 40 mm Hg until 40% of the maximal bleed-out volume was returned in the form of Ringer's lactate. The animals were then resusc itated with four times the volume of maximal bleed-out with RL over 60 minu tes, The ROS scavenger 2-mercaptopropionyl glycine (30 mg/kg) or vehicle wa s administered intravenously as a bolus at the beginning of resuscitation, At 2 hours after the completion of crystalloid resuscitation or the equival ent interval after sham-operation, cardiac index was measured by a dye dilu tion technique, Hepatocellular function, i,e,, the maximum velocity of indo cyanine green clearance (V-max) and the efficiency of the active transport (K-m), was determined using an in vivo hemoreflectometer, Serum levels of t umor necrosis factor (TNF)-alpha and alanine aminotransferase were determin ed with ELISA and colorimetrically, respectively, Results: The results indicate that at 2 hours after trauma hemorrhage and r esuscitation, cardiac index and hepatocellular function were markedly depre ssed with concomitantly increased serum levels of TNF-alpha and alanine ami notransferase (p < 0,05), Administration of 2-mercaptopropionyl glycine, ho wever, restored the depressed cardiac and hepatic function and markedly att enuated liver enzyme release and serum levels of TNF-<alpha> (p < 0,05), Conclusion: Our data suggest that ROS play a role in producing the depressi on in organ functions after severe hemorrhagic shock, Thus, adjuncts that a ttenuate the detrimental effects of ROS may be useful for improving the dep ressed cardiac and hepatocellular functions after trauma hemorrhage and res uscitation.