Evidence map›Paper›PMID 36362352›Full record

ArticleInternational journal of molecular sciences2022

Quantification of Cardiotonic Steroids Potentially Regulated by Paraoxonase 3 in a Rat Model of Chronic Kidney Disease Using UHPLC-Orbitrap-MS.

Sabitri Lamichhane, Chrysan J Mohammed, Steven T Haller, David J Kennedy, Dragan Isailovic

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 44% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. The Paraoxonase (International journal of molecular sciences · 2025
    Review
  2. Paraoxonases at the Heart of Neurological Disorders.International journal of molecular sciences · 2023
    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

5 authors at 1 institution in 1 country.

Sabitri LamichhaneDepartment of Chemistry and Biochemistry, University of Toledo, Toledo, OH 43606, USA.
Chrysan J MohammedDepartment of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
Steven T HallerDepartment of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.ORCID 0000-0002-6919-6342
David J KennedyDepartment of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.ORCID 0000-0001-5265-0142
Dragan IsailovicDepartment of Chemistry and Biochemistry, University of Toledo, Toledo, OH 43606, USA.
University of Toledo · US

Funding

Gene targeted rat resource for the study of complex diseaseR24HL114474 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI DWINELL, MELINDA R · 2013 to 2017
$8.7M
Counter regulatory mechanisms of cardiotonic steroids in cardio-renal syndromeR01HL137004 · NHLBI · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI KENNEDY, DAVID JOSEPH · 2017 to 2021
$1.9M
NHLBI NIH HHS R01 HL137004NHLBI NIH HHS R24 HL114474NIH HHS HL-137004NIH HHS R24HL114474
6 · The paper itself

Abstract

Endogenous cardiotonic steroids (CTSs), such as telocinobufagin (TCB) and marinobufagin (MBG) contain a lactone moiety critical to their binding and signaling through the Na+/K+-ATPase. Their concentrations elevate in response to sodium intake and under volume-expanded conditions. Paraoxonase 3 (PON3) is an enzyme that can hydrolyze lactone substrates. Here, we examine the role of PON3 in regulating CTS levels in a rat model of chronic kidney diseases (CKD). TCB and MBG were extracted from rat urine samples, and the analyses were carried out using ultra-high pressure liquid chromatography−Orbitrap-mass spectrometry (UHPLC-Orbitrap-MS). Ten-week-old Dahl salt-sensitive wild type (SS-WT) and Dahl salt-sensitive PON3 knockout (SS-PON3 KO) rats were maintained on a high-salt diet (8% NaCl) for 8 weeks to initiate salt-sensitive hypertensive renal disease characteristic of this model. CTS extraction recovery from urine >80% was achieved. For animals maintained on a normal chow diet, the baseline amount of TCB excreted in 24 h urine of SS-PON3 KO rats (6.08 ± 1.47 ng/24 h; or 15.09 ± 3.25 pmol) was significantly higher than for SS-WT rats (1.48 ± 0.69 ng/24 h; or 3.67 ± 1.54 pmol, p < 0.05). Similarly, for the same animals, the amount of excreted MBG was higher in the urine of SS-PON3 KO rats (4.74 ± 1.30 ng/24 h versus 1.03 ± 0.25 ng/24 h in SS-WT; or 11.83 ± 2.91 pmol versus 2.57 ± 0.56 pmol in SS-WT, p < 0.05). For animals on a high-salt diet, the SS-PON3 KO rats had significantly increased levels of TCB (714.52 ± 79.46 ng/24 h; or 1774.85 ± 175.55 pmol) compared to SS-WT control (343.84 ± 157.54 ng/24 h; or 854.09 ± 350.02 pmol, p < 0.05), and comparatively higher levels of MBG were measured for SS-PON3 KO (225.55 ± 82.61 ng/24 h; or 563.19 ± 184.5 pmol) versus SS-WT (157.56 ± 85.53 ng/24 h; or 393.43 ± 191.01 pmol, p > 0.05) rats. These findings suggest that the presence and absence of PON3 dramatically affect the level of endogenous CTSs, indicating its potential role in CTS regulation.

Indexed as

Cardiac GlycosidesHypertensionRenal Insufficiency, ChronicAnimalsAryldialkylphosphataseBlood PressureChromatography, High Pressure LiquidKidneyLactonesRatsRats, Inbred DahlSodium ChlorideSodium Chloride, DietarySodium-Potassium-Exchanging ATPaseAryldialkylphosphataseCardiac GlycosidesLactonesSodium ChlorideSodium Chloride, DietarySodium-Potassium-Exchanging ATPaseendogenous cardiotonic steroidsLC–MSmarinobufaginparaoxonaseSPEtelocinobufaginurine

Identifiers

PMID36362352
PMCPMC9654389
OpenAlexW4308509739

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.