Cited by 195Nitric Oxide and Endothelin EffectsDrug-Induced Hepatotoxicity and ProtectionLiver physiology and pathology

IV. Determinants of nitric oxide protection and toxicity in liver

Li, Jianrong, Billiar, Timothy R.·1999·American Journal of Physiology-Gastrointestinal and Liver Physiology

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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Registry

Crossref · 10.1152/ajpgi.1999.276.5.g1069

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25 of 25 references verified0 citation errors · 0 not checkable

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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)”
  • 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.”
  • 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”

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Authors
Li, J., & Billiar, T. R.
Affiliations
University of Pittsburgh (US)
Venue
American Journal of Physiology-Gastrointestinal and Liver Physiology
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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