Evidence map›Paper›PMID 22498344›Full record

ArticleDrug and alcohol dependence2012

An LC-MS/MS method for concurrent determination of nicotine metabolites and the role of CYP2A6 in nicotine metabolite-mediated oxidative stress in SVGA astrocytes.

Anusha Ande, Ravinder Earla, Mengyao Jin, Peter S Silverstein, Ashim K Mitra, Anil Kumar, Santosh Kumar

Abstract read
In one paragraph

Article in Drug and alcohol dependence, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

25 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Article
  3. Cigarette smoking and alcohol-related liver disease.Liver research (Beijing, China) · 2024
    Review
  4. Article
  5. Impact of Adolescent Nicotine Exposure in Pre- and Post-natal Oxycodone Exposed Offspring.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023
    Article
  6. Brain Energy Metabolism in Ischemic Stroke: Effects of Smoking and Diabetes.International journal of molecular sciences · 2022
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Mitochondria as a possible target for nicotine action.Journal of bioenergetics and biomembranes · 2019
    Review
  12. Nicotine enhances alcoholic fatty liver in mice: Role of CYP2A5.Archives of biochemistry and biophysics · 2018
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. RNA Viruses: ROS-Mediated Cell Death.International journal of cell biology · 2014
    Review
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

7 authors at 1 institution in 1 country.

Anusha AndePharmacology and Toxicology, School of Pharmacy, 3253 Health Sciences Building, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO 64108, USA.
Ravinder Earla
Mengyao Jin
Peter S Silverstein
Ashim K Mitra
Anil Kumar
Santosh Kumar
University of Missouri–Kansas City · US

Funding

Tobacco/nicotine, cytochrome P450, and HIV-1R21DA031616 · NIDA · UNIVERSITY OF MISSOURI KANSAS CITY · PI KUMAR, SANTOSH · 2011 to 2012
$413k
NIDA NIH HHS DA031616-01NIDA NIH HHS R21 DA031616
6 · The paper itself

Abstract

backgroundNicotine is known to generate oxidative stress through cytochrome P450 2A6 (CYP2A6)-mediated metabolism in the liver and other organs, including macrophages. This study has been designed to examine the role of CYP2A6 in nicotine metabolism and oxidative stress in SVGA cells, an immortalized human astrocyte cell line.

methodsSVGA astrocytes were treated with 1 μM nicotine, followed by determination of mRNA and protein levels of several CYPs using quantitative RT-PCR and western blot analyses, respectively. Quantitation of nicotine and the nicotine metabolites, cotinine and nicotine-derived nitrosamine ketones (NNK), was performed using an LC-MS/MS method. The generation of reactive oxygen species (ROS) was measured using flow cytometry.

resultsNicotine significantly upregulated mRNA and protein expression of the most abundantly expressed CYPs in SVGA astrocytes, CYP2A6 and CYP1A1. To characterize the metabolism of nicotine in astrocytes, a highly sensitive LC-MS/MS method was developed which is capable of quantifying very low concentrations of nicotine (0.3 ng/mL), cotinine and NNK (0.11 ng/mL). The LC-MS/MS results showed that nicotine is steadily metabolized to cotinine and NNK from 0.5 to 4h. Finally, we showed that nicotine initially causes an increase in ROS formation which is then gradually decreased, perhaps due to the increase in superoxide dismutase level. Nicotine metabolism and ROS formation by CYP2A6 were further confirmed by using tryptamine, a selective inhibitor of CYP2A6, which significantly lowered the levels of cotinine and NNK and inhibited ROS formation.

conclusionsCYP2A6 plays a key role in nicotine metabolism and oxidative stress in astrocytes, and this has implications in nicotine-associated brain toxicity.

Indexed as

Aryl Hydrocarbon HydroxylasesAstrocytesBlotting, WesternCell LineChromatography, High Pressure LiquidCotinineCytochrome P-450 CYP1A1Cytochrome P-450 CYP2A6Enzyme InductionHumansKetonesLimit of DetectionNicotineNicotinic AgonistsNitrosaminesOxidative StressAryl Hydrocarbon HydroxylasesCotinineCYP2A6 protein, humanCytochrome P-450 CYP1A1Cytochrome P-450 CYP2A6KetonesNicotineNicotinic AgonistsNitrosaminesReactive Oxygen SpeciesRNA

Identifiers

PMID22498344
PMCPMC3413753
OpenAlexW2015207436

What OpenQuestion holds

Textmetadata
LicenceTDM
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.