Evidence map›Paper›PMID 29858698›Full record

ArticleThe AAPS journal2018

Evaluation of 4β-Hydroxycholesterol and 25-Hydroxycholesterol as Endogenous Biomarkers of CYP3A4: Study with CYP3A-Humanized Mice.

Shin-Ichiro Nitta, Mari Hashimoto, Yasuhiro Kazuki, Shoko Takehara, Hiraku Suzuki, Mitsuo Oshimura, Hidetaka Akita, Kan Chiba, Kaoru Kobayashi

Abstract read
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In one paragraph

Article in The AAPS journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

11 citing papers in PubMed, 20 citations in OpenAlex.

  1. Serum 4β-hydroxycholesterol increases during fluconazole treatment.European journal of clinical pharmacology · 2021
    Trial
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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

9 authors at 2 institutions in 1 country.

Shin-Ichiro NittaLaboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan.
Mari HashimotoLaboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan.
Yasuhiro KazukiDepartment of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan.
Shoko TakeharaChromosome Engineering Research Center (CERC), Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan.
Hiraku SuzukiLSI Medience Corporation, 3-30-1 Shimura, Itabashi-ku, Tokyo, 174-8555, Japan.
Mitsuo OshimuraChromosome Engineering Research Center (CERC), Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan.
Hidetaka AkitaLaboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan.
Kan ChibaLaboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan.
Kaoru KobayashiLaboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan. kaoruk@facutly.chiba-u.jp.
Chiba University · JPTottori University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cytochrome P450 3A (CYP3A) enzymes metabolize approximately half of all drugs on the market. Since the endogenous compounds 4β-hydroxycholesterol (4β-HC) and 25-hydroxycholesterol (25-HC) are generated from cholesterol via CYP3A enzymes, we examined whether the plasma levels of 4β-HC and 25-HC reflect hepatic CYP3A4 activity by using a CYP3A-humanized mouse model, in which the function of endogenous Cyp3a was genetically replaced by human CYP3A. CYP3A-humanized mice have great advantages for evaluation of the relationship between hepatic CYP3A protein levels and plasma and hepatic levels of 4β-HC and 25-HC. Levels of CYP3A4 protein in the liver microsomes of CYP3A-humanized mice were increased by treatment with pregnenolone-16α-carbonitrile, a CYP3A inducer. Hepatic and plasma levels of 4β-HC and 25-HC normalized by cholesterol were significantly correlated with hepatic CYP3A4 protein levels. In addition, in vitro studies using human liver microsomes showed that the formation of 4β-HC was strongly inhibited by a CYP3A inhibitor, while the inhibitory effect of the CYP3A inhibition on the formation of 25-HC was weak. These results suggested that CYP3A mainly contributed to the formation of 4β-HC in human liver microsomes, whereas other factors may be involved in the formation of 25-HC. In conclusion, the in vivo studies using CYP3A-humanized mice suggest that plasma 4β-HC and 25-HC levels reflect hepatic CYP3A4 activity. Furthermore, taking the results of in vitro studies using human liver microsomes into consideration, 4β-HC is a more reliable biomarker of hepatic CYP3A activity.

Indexed as

AnimalsBiomarkersChromatography, LiquidCytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemHumansHydroxycholesterolsMaleMembrane ProteinsMiceMicrosomes, LiverTandem Mass Spectrometry25-hydroxycholesterolBiomarkerscholest-5-ene-3,4-diolCyp3a11 protein, mouseCYP3A4 protein, humanCytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemHydroxycholesterolsMembrane Proteins25-hydroxycholesterol4β-hydroxycholesterolbiomarkerCYP3A4LC-MS/MS

Identifiers

PMID29858698
OpenAlexW2797994387

What Socratic holds

Textmetadata
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 Socratic graph.