Interleukin 1-induced production of nitric oxide inhibits benzenetriol-mediated oxidative injury in rat hepatocytes.
OBJECTIVE
Nitric oxide modifies free radical-mediated cell processes in multiple in vivo and in vitro systems. The aim of this study was to determine the role of hepatocyte production of NO in oxidative injury.


METHODS
Rat hepatocytes in primary culture were incubated with 1,2,3-benzenetriol, a source of superoxide. Interleukin (IL) 1 was added to induce NO synthesis. Injury was determined by aspartate aminotransferase (AST), malondialdehyde (MDA), and glutathione (GSH) levels.


RESULTS
Benzenetriol-induced injury increased AST and MDA levels and decreased GSH levels in control and IL-1-treated cells. Inhibition of NO synthesis in IL-1-treated cells significantly increased AST and MDA production while enhancing GSH depletion. In the presence of superoxide dismutase or S-nitroso-albumin, an exogenous source of NO, injury was decreased or abolished. NO production was significantly increased with oxidative stress. In benzenetriol-induced injury in IL-1-stimulated hepatocytes, reverse-transcription polymerase chain reaction showed significantly increased levels of inducible NO synthase messenger RNA, whereas immunoblot analysis showed similarly increased levels of inducible NO synthase protein.


CONCLUSIONS
In this rat hepatocyte model of IL-1/benzenetriol-mediated injury, NO, derived from endogenous synthesis or an exogenous donor, is protective. Oxidative stress may have a role in the transcriptional control of NO synthesis.
Kuo
P C
PC
Department of Surgery, Stanford University Medical Center, California, USA.
Abe
K Y
KY
D000594:Amino Acid Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002478:Cells, Cultured; D005978:Glutathione / Q000378:metabolism; D006873:Hydroquinones / Q000009:adverse effects*; D007375:Interleukin-1 / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D018384:Oxidative Stress / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D006873:Hydroquinones; D007375:Interleukin-1; D012333:RNA, Messenger; D013481:Superoxides; C013038:hydroxyhydroquinone; D009569:Nitric Oxide; D008315:Malondialdehyde; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D000594:Amino Acid Oxidoreductases; D001219:Aspartate Aminotransferases; D005978:Glutathione