Evidence map›Paper›PMID 30406478›Full record

ArticlePharmaceutical research2018

An Expandable Mechanopharmaceutical Device (2): Drug Induced Granulomas Maximize the Cargo Sequestering Capacity of Macrophages in the Liver.

Phillip Rzeczycki, Gi Sang Yoon, Rahul K Keswani, Sudha Sud, Jason Baik, Mikhail D Murashov, Ingrid L Bergin, Kathleen A Stringer, Gus R Rosania

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmaceutical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 28% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Article
  3. Molecular design of a pathogen activated, self-assembling mechanopharmaceutical device.Journal of controlled release : official journal of the Controlled Release Society · 2022
    Review
  4. Article
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 1 institution in 1 country.

Phillip RzeczyckiDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan, 48109, USA.
Gi Sang YoonDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan, 48109, USA.
Rahul K KeswaniDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan, 48109, USA.
Sudha SudDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan, 48109, USA.
Jason BaikDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan, 48109, USA.
Mikhail D MurashovDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan, 48109, USA.
Ingrid L BerginUnit for Laboratory Animal Medicine, Medical School Office of Research, University of Michigan, 2800 Plymouth Road, Ann Arbor, Michigan, 48109, USA.
Kathleen A StringerDepartment of Clinical Pharmacy, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan, 48104, USA.
Gus R RosaniaDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan, 48109, USA. grosania@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Chemical Address Tags: A Cheminformatics & Image Data Management and Analysis Plan - SupplementR01GM078200 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROSANIA, GUS R · 2006 to 2015
$4.2M
L-Carnitine Pharmacometabolomics in Sepsis (CaPS)R01GM111400 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI STRINGER, KATHLEEN A · 2016 to 2019
$1.2M
National Institutes of Health R01GM078200NIGMS NIH HHS R01 GM078200NIGMS NIH HHS R01 GM111400
6 · The paper itself

Abstract

purposeDrug-induced liver injuries (DILI) comprise a significant proportion of adverse drug reactions leading to hospitalizations and death. One frequent DILI is granulomatous inflammation from exposure to harmful metabolites that activate inflammatory pathways of immune cells of the liver, which may act as a barrier to isolate the irritating stimulus and limit tissue damage.

methodsParalleling the accumulation of CFZ precipitates in the liver, granulomatous inflammation was studied to gain insight into its effect on liver structure and function. A structural analog that does not precipitate within macrophages was also studied using micro-analytical approaches. Depleting macrophages was used to inhibit granuloma formation and assess its effect on drug bioaccumulation and toxicity.

resultsGranuloma-associated macrophages showed a distinct phenotype, differentiating them from non-granuloma macrophages. Granulomas were induced by insoluble CFZ cargo, but not by the more soluble analog, pointing to precipitation being a factor driving granulomatous inflammation. Granuloma-associated macrophages showed increased activation of lysosomal master-regulator transcription factor EB (TFEB). Inhibiting granuloma formation increased hepatic necrosis and systemic toxicity in CFZ-treated animals.

conclusionsGranuloma-associated macrophages are a specialized cell population equipped to actively sequester and stabilize cytotoxic chemotherapeutic agents. Thus, drug-induced granulomas may function as drug sequestering "organoids" -an induced, specialized sub-compartment- to limit tissue damage.

Indexed as

Chemical and Drug Induced Liver InjuryAnimalsClofazimineDrug Delivery SystemsGranulomaLiverMacrophagesMaleMiceClofazimineBiocrystalclofaziminegranulomamacrophageTFEB

Identifiers

PMID30406478
PMCPMC6506721
OpenAlexW2899539954

What OpenQuestion holds

Textmetadata
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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.