IV. Determinants of nitric oxide protection and toxicity in liver
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.
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The biological role of the oxygen-regulated oxidative-to-reductive transition is particularly prominent for heme- and molybdopterin-containing proteins such as hemoglobin, myoglobin, and xanthine oxidase.
“The biological role of this transition is particularly prominent in the case of heme- and molybdopterin-containing proteins such as hemoglobin (Hb), myoglobin (Mb), and xanthine oxidase (XO)”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [578]
A number of proteins involved in oxidative processes at basal oxygen levels can become de facto reductases as oxygen is depleted.
“However, a number of proteins that are involved in oxidative processes at basal oxygen levels can become de facto reductases as oxygen is depleted.”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [578]
Oxygen levels can impact the oxidation/reduction properties of different proteins and regulate NO levels.
“In this context, it has become increasingly appreciated that oxygen levels can impact the oxidation/reduction properties of different proteins and regulate NO levels”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [578]
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- Authors
- Li, J., & Billiar, T. R.
- Affiliations
- University of Pittsburgh (US)
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 1999-05-01
- Volume
- 276
- Issue
- 5
- Pages
- G1069-G1073
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W2175315926
- Cited by
- 195
- References
- 25
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 5 · 2013: 8 · 2012: 10
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM 37753, GM-44100, R01GM037753)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- nitric oxide, inducible nitric oxide synthase, endothelial nitric oxide synthase, hepatoprotection, hepatotoxicity, redox stress, apoptosis inhibition, cytokines, liver inflammation, iNOS inhibitors
- MeSH terms
- Animals, Humans, Liver, Nitric Oxide, Oxidation-Reduction, Nitric Oxide Synthase, Mice, Nitric Oxide Synthase Type II, Chemical and Drug Induced Liver Injury
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