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Nitric Oxide. IV. Determinants of nitric oxide protection and toxicity in liver
1Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Abstract:
Whereas nitric oxide (NO) produced by constitutive endothelial NO synthase is protective to the liver, NO produced by the inducible NO synthase (iNOS) can be either toxic or protective depending on the conditions. The availability of selective iNOS inhibitors and mice lacking various NOS isoforms made it possible to begin to elucidate the precise roles of NO in the liver. Under conditions of redox stress, induced NO contributes to hepatic damage. However, in acute inflammatory conditions associated with cytokine exposure, NO acts as a potent inhibitor of apoptosis in the liver. Our current understanding of the mechanisms by which NO exerts both hepatoprotective and hepatotoxic actions is discussed in this themes article.
Insights
Nitric oxide (NO) from inducible NO synthase (iNOS) can harm or protect the liver. Research clarifies iNOS
Area of Science:
- Hepatology
- Molecular Biology
- Biochemistry
Background:
- Nitric oxide (NO) plays a dual role in liver function, with constitutive endothelial NO synthase (eNOS) being protective.
- Inducible NO synthase (iNOS)-derived NO can be hepatotoxic or hepatoprotective, depending on the physiological context.
- Understanding iNOS-specific roles is crucial for liver disease research.
Purpose of the Study:
- To elucidate the precise roles of NO in the liver, particularly focusing on iNOS.
- To discuss the mechanisms underlying NO-mediated hepatoprotection and hepatotoxicity.
Main Methods:
- Utilized selective iNOS inhibitors.
- Employed genetically modified mice lacking various NOS isoforms.
- Investigated NO's effects under conditions of redox stress and acute inflammation.
Main Results:
- Induced NO contributes to hepatic damage under redox stress conditions.
- NO potently inhibits apoptosis in the liver during acute inflammatory responses.
- Demonstrated context-dependent functions of iNOS-derived NO in the liver.
Conclusions:
- iNOS-derived NO exhibits dichotomous effects on liver injury and protection.
- NO's role in hepatic apoptosis is context-dependent, acting as an inhibitor during inflammation.
- Further research into NO signaling pathways is essential for therapeutic strategies.