Evidence map›Paper›PMID 27194299›Full record

ArticleMolecular neurobiology2017

Anesthetic Isoflurane Induces DNA Damage Through Oxidative Stress and p53 Pathway.

Cheng Ni, Cheng Li, Yuanlin Dong, Xiangyang Guo, Yiying Zhang, Zhongcong Xie

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurobiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

26 citing papers in PubMed, 57 citations in OpenAlex.

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  9. Neonatal Anesthesia and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2022
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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

6 authors at 3 institutions in 2 countries.

Cheng NiDepartment of Anesthesiology, Peking University Third Hospital, 49 North Garden Rd., Haidian District, Beijing, 100191, China.
Cheng LiGeriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA, 02129, USA.
Yuanlin DongGeriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA, 02129, USA.
Xiangyang GuoDepartment of Anesthesiology, Peking University Third Hospital, 49 North Garden Rd., Haidian District, Beijing, 100191, China.
Yiying ZhangGeriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA, 02129, USA.
Zhongcong XieGeriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA, 02129, USA. zxie@mgh.harvard.edu.
Massachusetts General Hospital · USHarvard University · USPeking University · CN

Funding

Pathogenesis of Postoperative Cognitive DysfunctionR01AG041274 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Zhongcong Xie, Guang Yang · 2012 to 2026
$6.7M
General Anesthesia and Alzheimer's Disease NeuropathogenesisR01GM088801 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI XIE, ZHONGCONG · 2009 to 2017
$3.1M
Tau/P-Tau as Biomarkers of Anesthesia- and Surgery-Induced Cognitive Impairment in a Murine ModelR01HD086977 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI XIE, ZHONGCONG · 2016 to 2020
$1.8M
The Role of Alzheimer's-associated Abeta in POD and POCDR21AG038994 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI XIE, ZHONGCONG · 2011 to 2012
$412k
NIA NIH HHS R01 AG041274NIA NIH HHS R21 AG038994NICHD NIH HHS R01 HD086977NIGMS NIH HHS R01 GM088801
6 · The paper itself

Abstract

DNA damage is associated with aging and neurological disorders, including Alzheimer's disease. Isoflurane is a commonly used anesthetic. It remains largely unknown whether isoflurane induces DNA damage. Phosphorylation of the histone protein H2A variant X at Ser139 (γH2A.X) is a marker of DNA damage. We therefore set out to assess the effects of isoflurane on γH2A.X level in H4 human neuroglioma cells and in brain tissues of mice. Oxidative stress, caspase-activated DNase (CAD), and the p53 signaling pathway are involved in DNA damage. Thus, we determined the interaction of isoflurane with reactive oxygen species (ROS), CAD, and p53 to illustrate the underlying mechanisms. The cells were treated with 2 % isoflurane for 3 or 6 h. The mice were anesthetized with 1.4 % isoflurane for 2 h. Western blot, immunostaining and live cell fluorescence staining were used in the experiments. We showed that isoflurane increased levels of γH2A.X, cleaved caspase-3, and nucleus translocation of CAD and decreased levels of inhibitor of CAD (ICAD) and p53. Isoflurane enhanced the nucleus level of γH2A.X. Moreover, caspase inhibitor Z-VAD and ROS generation inhibitor N-acetyl-L-cysteine (NAC) attenuated the isoflurane-induced increase in γH2A.X level. However, NAC did not significantly alter the isoflurane-induced reduction in p53 level. Finally, p53 activator (actinomycin D) and inhibitor (pifithrin-α) attenuated and potentiated the isoflurane-induced increase in γH2A.X level, respectively. These findings suggest that isoflurane might induce DNA damage, as represented by increased γH2A.X level, via induction of oxidative stress and inhibition of the repair of DNA damage through the p53 signaling pathway.

Indexed as

DNA DamageAcetylcysteineAnesthetics, InhalationAnimalsBenzothiazolesBrainCaspase 3Cell Line, TumorCytosolDactinomycinDeoxyribonucleasesEnzyme ActivationHistonesHumansIsofluraneMiceAcetylcysteineAnesthetics, InhalationBenzothiazolesbenzyloxycarbonyl-valyl-alanyl-aspartic acidCaspase 3caspase-activated deoxyribonucleaseDactinomycinDeoxyribonucleasesH2AX protein, humanHistonesIsofluraneOligopeptidespifithrinTolueneTumor Suppressor Protein p53AnesthesiaCaspase-3DNA damagep53ROS

Identifiers

PMID27194299
PMCPMC5736399
OpenAlexW2399632048

What OpenQuestion holds

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Read underepoch 390

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.