Evidence map›Paper›PMID 33735324›Full record

ArticlePloS one2021

Low-dose hydralazine during gestation reduces renal fibrosis in rodent offspring exposed to maternal high fat diet.

Benjamin P Larkin, Sonia Saad, Sarah J Glastras, Long T Nguyen, Miao Hou, Hui Chen, Rosy Wang, Carol A Pollock

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

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
5.0field-weighted citation impact, top 5% 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

13 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Review
  3. Oxidative Stress in Fetuses and Newborns.Antioxidants (Basel, Switzerland) · 2024
    Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Chronic Kidney Disease: Strategies to Retard Progression.International journal of molecular sciences · 2021
    Review
  11. The Zebrafish Model to Understand Epigenetics in Renal Diseases.International journal of molecular sciences · 2021
    Review
  12. Review
  13. 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

8 authors at 3 institutions in 2 countries.

Benjamin P LarkinRenal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia.
Sonia SaadRenal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia.
Sarah J GlastrasRenal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia.
Long T NguyenRenal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia.
Miao HouDepartment of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China.
Hui ChenSchool of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, Australia.
Rosy WangRenal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia.
Carol A PollockRenal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia.
University of Sydney · AUUniversity of Technology Sydney · AUSoochow University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMaternal high fat diet (HFD) promotes chronic kidney disease (CKD) in offspring. This is in accordance with the theory of fetal programming, which suggests adverse conditions occurring in utero predispose offspring to chronic conditions later in life. DNA methylation has been proposed as a key mechanism by which fetal programming occurs and is implicated in CKD progression. DNA demethylating drugs may interrupt the fetal programming of CKD by maternal obesity. Hydralazine, an antihypertensive agent, demethylates DNA at low doses which do not reduce blood pressure. We used a mouse model of maternal obesity to determine whether gestational administration of low-dose hydralazine to mothers can prevent CKD in offspring.

methodsC57BL/6 dams received HFD or chow from 6 weeks prior to mating and were administered subcutaneous hydralazine (5mg/kg) or saline thrice weekly during gestation. Male offspring were weaned to chow and were sacrificed at either postnatal week 9 or week 32. Biometric and metabolic parameters, renal global DNA methylation, renal structural and functional changes and markers of fibrosis, oxidative stress and inflammation were measured in offspring at weeks 9 and 32.

resultsIn week 9 offspring, maternal HFD consumption did not significantly alter anthropometric or metabolic parameters, or renal global DNA methylation. Week 32 offspring had increased renal global DNA methylation, together with albuminuria, glomerulosclerosis, renal fibrosis and oxidative stress. Administration of low-dose hydralazine to obese mothers during gestation reduced renal global DNA methylation and renal fibrotic markers in week 32 offspring.

conclusionGestational hydralazine reduced renal global DNA methylation in offspring of obese mothers and attenuated maternal obesity-induced renal fibrosis. These data support the use of low-dose hydralazine as a demethylating agent to prevent CKD arising in offspring due to maternal HFD consumption.

Indexed as

Diet, High-FatAlbuminuriaAnimalsBiomarkersBody WeightCollagenDNA MethylationFemaleFibronectinsFibrosisHydralazineInflammationKidneyKidney GlomerulusMiceMice, Inbred C57BLBiomarkersCollagenFibronectinsHydralazine

Identifiers

PMID33735324
PMCPMC7971884
OpenAlexW3139460872

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.