21-Aminosteroids block neutrophil infiltration and provide liver protection independent of NO2-/NO3- levels.

21-Aminosteroids are antioxidant compounds that prevent iron-dependent lipid peroxidation and improve cell viability. In this work we attempt to define the role of 21-aminosteroids in liver ischemia and reperfusion and assess their possible mode of action, specifically their effect on neutrophil infiltration and nitrite/nitrate levels. Total liver ischemia for 90 min was produced in the rat with the use of a portosystemic shunt. Three groups of animals were studied. One group received the 21-aminosteroid U-74389G (10 mg/ kg) divided into two equal doses 10 min prior to ischemia (7 mg/kg) and 10 min before reperfusion (3 mg/ kg). The two other groups included the sham and the control animals. We studied survival at 7 days and serum liver enzymes, liver myeloperoxidase, plasma nitrites, nitrates, and liver histology at 6 hr postreperfusion. Animal survival improved from 13% in the ischemic control to 52% in the lazaroid treated group (P < 0.05). We observed significant improvements in liver function tests, liver myeloperoxidase levels, as well as in the liver histology (P < 0.05). We could not find statistical difference in plasma nitrite/nitrate (P > 0.1). The 21-aminosteroids significantly improved animal survival after total liver ischemia, through a mechanism that includes blocking neutrophil infiltration which is independent from nitrite/nitrate levels.