Interleukin 1-induced production of nitric oxide inhibits benzenetriol-mediated oxidative injury in rat hepatocytes.
BACKGROUND & AIMS: 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.
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- Superoxides
- Superoxide Dismutase
- Rats, Inbred Lew
- Rats
- RNA, Messenger
- Polymerase Chain Reaction
- Oxidative Stress
- Nitric Oxide Synthase
- Nitric Oxide
- Malondialdehyde
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Superoxides
- Superoxide Dismutase
- Rats, Inbred Lew
- Rats
- RNA, Messenger
- Polymerase Chain Reaction
- Oxidative Stress
- Nitric Oxide Synthase
- Nitric Oxide
- Malondialdehyde