The amelioration of hepatocyte oxidative stress injury by nitric oxide released from S-nitroso-N-acetyl penicillamine: A study in immobilized perfused hepatocytes

S-nitroso-N-acetyl penicillamine (SNAP, 0.1-0.5 mM) caused release of nitri c oxide (NO) into the perfusion medium of immobilized hepatocytes. Oxidativ e injury of hepatocytes was evoked by tert-butyl hydroperoxide (TBH, 1 mM) and the functional and morphological ultrastructural integrity of the the c ells was monitored. At the end of a 270-min perfusion period, SNAP-induced NO reduced lactate dehydrogenase leakage in TBH-injured heparocytes as comp ared to untreated TBH-injured cells (122% +/- 5 vs. 146% +/- 6 of control c ontrol levels), lipid peroxides production (2.7 +/- 0.2 vs. 3.7 +/- 0.3 nmo l/10(6) cells), increased O-2 consumption (26 +/- 2 vs. 12 +/- 1 nmol/10(6) cells) although urea synthesis was reduced. SNAP improved the formation of granules in the Golgi complex as compared to untreated TBX-injured hepatoc ytes and preserved the ultrastructural architecture mitochondria and the sm ooth endoplasmic reticulum. The present data support a possible protective role of NO in oxidative liver injury. (C)1999 Prous Science. All rights res erved.