ArticleFree radical biology & medicine2015
The neuronal nitric oxide synthase inhibitor NANT blocks acetaminophen toxicity and protein nitration in freshly isolated hepatocytes.
Article in Free radical biology & medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Reactive oxygen species and peroxynitrite in acetaminophen-induced liver injury: Lipid peroxidation and ferroptosis-like cell death.Ferroptosis and oxidative stress · 2026Article
- The compartmentalization model of nitrate homeostasis: Role of the salivary glands, skeletal muscle, and liver.EXCLI journal · 2026Review
- Inhibition of hepatic gluconeogenesis in type 2 diabetes by metformin: complementary role of nitric oxide.Medical gas research · 2025Review
- Central Mechanisms of Acetaminophen Hepatotoxicity: Mitochondrial Dysfunction by Protein Adducts and Oxidant Stress.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Acetaminophen Hepatotoxicity: Paradigm for Understanding Mechanisms of Drug-Induced Liver Injury.Annual review of pathology · 2024Review
- Peli3 ablation ameliorates acetaminophen-induced liver injury through inhibition of GSK3β phosphorylation and mitochondrial translocation.Experimental & molecular medicine · 2023Article
- Platanosides, a Potential Botanical Drug Combination, Decrease Liver Injury Caused by Acetaminophen Overdose in Mice.Journal of natural products · 2022Review
- The role of Iron in lipid peroxidation and protein nitration during acetaminophen-induced liver injury in mice.Toxicology and applied pharmacology · 2022Article
- Ferroptosis and Acetaminophen Hepatotoxicity: Are We Going Down Another Rabbit Hole?Gene expression · 2021Review
- Post-treatment with glycyrrhizin can attenuate hepatic mitochondrial damage induced by acetaminophen in mice.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- The development and hepatotoxicity of acetaminophen: reviewing over a century of progress.Drug metabolism reviews · 2020Review
- A mitochondrial journey through acetaminophen hepatotoxicity.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2020Review
- Novel Therapeutic Approaches Against Acetaminophen-induced Liver Injury and Acute Liver Failure.Toxicological sciences : an official journal of the Society of Toxicology · 2020Review
- C/EBPδ protects from radiation-induced intestinal injury and sepsis by suppression of inflammatory and nitrosative stress.Scientific reports · 2019Article
- Hepatic nitric oxide synthase 1 adaptor protein regulates glucose homeostasis and hepatic insulin sensitivity in obese mice depending on its PDZ binding domain.EBioMedicine · 2019Article
- Acetaminophen Hepatotoxicity.Seminars in liver disease · 2019Article
- Acetaminophen hepatotoxicity: A mitochondrial perspective.Advances in pharmacology (San Diego, Calif.) · 2019Review
- PCB11 Metabolite, 3,3'-Dichlorobiphenyl-4-ol, Exposure Alters the Expression of Genes Governing Fatty Acid Metabolism in the Absence of Functional Sirtuin 3: Examining the Contribution of MnSOD.Antioxidants (Basel, Switzerland) · 2018Article
- Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives.Journal of clinical and translational research · 2018Review
- Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury.Antioxidants (Basel, Switzerland) · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
3-Nitrotyrosine (3NT) in liver proteins of mice treated with hepatotoxic doses of acetaminophen (APAP) has been postulated to be causative in toxicity. Nitration is by a reactive nitrogen species formed from nitric oxide (NO). The source of the NO is unclear. iNOS knockout mice were previously found to be equally susceptible to APAP toxicity as wildtype mice and iNOS inhibitors did not decrease toxicity in mice or in hepatocytes. In this work we examined the potential role of nNOS in APAP toxicity in hepatocytes using the specific nNOS inhibitor NANT (10 µM)(N-[(4S)-4-amino-5-[(2-aminoethyl)amino]pentyl]-N'-nitroguanidinetris (trifluoroacetate)). Primary hepatocytes (1 million/ml) from male B6C3F1 mice were incubated with APAP (1mM). Cells were removed and assayed spectrofluorometrically for reactive nitrogen and oxygen species using diaminofluorescein (DAF) and Mitosox red, respectively. Cytotoxicity was determined by LDH release into media. Glutathione (GSH, GSSG), 3NT, GSNO, acetaminophen-cysteine adducts, NAD, and NADH were measured by HPLC. APAP significantly increased cytotoxicity at 1.5-3.0 h. The increase was blocked by NANT. NANT did not alter APAP mediated GSH depletion or acetaminophen-cysteine adducts in proteins which indicated that NANT did not inhibit metabolism. APAP significantly increased spectroflurometric evidence of reactive nitrogen and oxygen formation at 0.5 and 1.0 h, respectively, and increased 3NT and GSNO at 1.5-3.0 h. These increases were blocked by NANT. APAP dramatically increased NADH from 0.5-3.0 h and this increase was blocked by NANT. Also, APAP decreased the Oxygen Consumption Rate (OCR), decreased ATP production, and caused a loss of mitochondrial membrane potential, which were all blocked by NANT.
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