Evidence map›Paper›PMID 33436521›Full record

ArticleMolecular pharmacology2021

A Potential Role for SerpinA3N in Acetaminophen-Induced Hepatotoxicity.

Melanie Tran, Jianguo Wu, Li Wang, Dong-Ju Shin

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.7field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 10 citations in OpenAlex.

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  4. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Melanie TranDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut (M.T., J.W., D.-J.S.) and Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut (L.W.) metran@uchc.edu dong-ju.shin@uconn.edu.
Jianguo WuDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut (M.T., J.W., D.-J.S.) and Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut (L.W.).
Li WangDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut (M.T., J.W., D.-J.S.) and Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut (L.W.).
Dong-Ju ShinDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut (M.T., J.W., D.-J.S.) and Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut (L.W.) metran@uchc.edu dong-ju.shin@uconn.edu.
University of Connecticut · USYale University · US

Funding

The microRNA Control of Alcoholic Liver Injury and Hepatic Lipid MetabolismR01AA026322 · NIAAA · UNIVERSITY OF CONNECTICUT STORRS · PI SHIN, DONG JU · 2017 to 2021
$1.8M
NIAAA NIH HHS R01 AA026322
6 · The paper itself

Abstract

Acetaminophen (APAP) is a commonly used pain and fever reliever but is also the most frequent cause of drug-induced liver injury. The mechanism pertaining acetaminophen toxicity has been well documented, whereas mechanisms of hepatotoxicity are not well established. Serine (or cysteine) peptidase inhibitor, clade A, member 3N (SerpinA3N), a serine protease inhibitor, is synthesized in the liver but the role of SerpinA3N in relation to APAP-induced liver injury is not known. Wild-type and hepatocyte-specific SerpinA3N knockout (HKO) mice were injected intraperitoneally with a single dose of PBS or APAP (400 mg/kg) for 12 hours, and markers of liver injury, cell death, and inflammation were assessed. SerpinA3N expression was highly induced in mice with APAP overdose. SerpinA3N HKO mice had diminished liver injury and necrosis as shown by lower alanine aminotransferase and interleukin-6 levels, accompanied by suppressed inflammatory cytokines and reduced neutrophil infiltration. The reduced oxidative stress was associated with enhanced antioxidant enzyme capabilities. Taken together, hepatocyte SerpinA3N deficiency reduced APAP-induced liver injury by ameliorating inflammation and modulating the 5' AMP-activated protein kinase-unc-51-like autophagy activating kinase 1 signaling pathway. Our study provides novel insights into a potential role for SerpinA3N in APAP-induced liver injury. SIGNIFICANCE STATEMENT: Our studies indicate that serine (or cysteine) peptidase inhibitor, clade A, member 3N (SerpinA3N) may have a pathophysiological role in modulating acetaminophen (APAP)-induced liver injury. More specifically, mice with hepatic deletion of SerpinA3N suppressed inflammation and liver injury to reduce APAP-induced hepatotoxicity. Controlling the inflammatory response offers possible approaches for novel therapeutics; therefore, understanding the pathophysiological role of SerpinA3N in inducing liver injury may add to the development of more efficacious treatments.

Indexed as

AcetaminophenAcute-Phase ProteinsAnalgesics, Non-NarcoticAnimalsChemical and Drug Induced Liver InjuryMaleMiceMice, 129 StrainMice, Inbred C57BLMice, KnockoutSerpinsAcetaminophenAcute-Phase ProteinsAnalgesics, Non-NarcoticSerpina3n protein, mouseSerpins

Identifiers

PMID33436521
PMCPMC7985612
OpenAlexW3118983279

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.