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 nitric oxide (NO) into the perfusion medium of immobilized hepatocytes. Oxidative injury of hepatocytes was evoked by tert-butyl hydroperoxide (TBH, 1 mM) and the functional and morphological ultrastructural integrity of the cells was monitored. At the end of a 270-min perfusion period, SNAP-induced NO reduced lactate dehydrogenase leakage in TBH-injured hepatocytes as compared to untreated TBH-injured cells (122% +/- 5 vs. 146% +/- 6 of control levels), lipid peroxides production (2.7 +/- 0.2 vs. 3.7 +/- 0.3 nmol/10(6) cells), increased O2 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 TBH-injured hepatocytes and preserved the ultrastructural architecture of mitochondria and the smooth endoplasmic reticulum. The present data support a possible protective role of NO in oxidative liver injury.
Farghali
H
H
Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague, Czech Republic. hfarg@lfl.cuni.cz
Martínek
J
J
Masek
K
K
D000818:Animals; D018914:Cells, Immobilized; D056486:Chemical and Drug Induced Liver Injury; D005688:Galactosamine / Q000633:toxicity; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000493:pharmacokinetics / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D020122:tert-Butylhydroperoxide / Q000633:toxicity
D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D005688:Galactosamine; D020122:tert-Butylhydroperoxide; D010396:Penicillamine