TMAO, a seafood-derived molecule, produces diuresis and reduces mortality in heart failure rats

  1. Marta Gawrys-Kopczynska
  2. Marek Konop
  3. Klaudia Maksymiuk
  4. Katarzyna Kraszewska
  5. Ladislav Derzsi
  6. Krzysztof Sozanski
  7. Robert Holyst
  8. Marta Pilz
  9. Emilia Samborowska
  10. Leszek Dobrowolski
  11. Kinga Jaworska
  12. Izabella Mogilnicka
  13. Marcin Ufnal  Is a corresponding author
  1. Medical University of Warsaw, Poland
  2. Institute of Physical Chemistry, Polish Academy of Sciences, Poland
  3. Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Poland
  4. M Mossakowski Medical Research Centre, Polish Academy of Sciences, Poland

Abstract

Trimethylamine-oxide (TMAO) is present in seafood which is considered to be beneficial for health. Deep-water animals accumulate TMAO to protect proteins, such as lactate dehydrogenase (LDH), against hydrostatic pressure stress (HPS). We hypothesized that TMAO exerts beneficial effects on the circulatory system and protects cardiac LDH exposed to HPS produced by the contracting heart. Male, Sprague-Dawley and Spontaneously-Hypertensive-Heart-Failure (SHHF) rats were treated orally with either water (control) or TMAO. In vitro, LDH with or without TMAO was exposed to HPS and was evaluated using fluorescence correlation spectroscopy. TMAO-treated rats showed higher diuresis and natriuresis, lower arterial pressure and plasma NT-proBNP. Survival in SHHF-control was 66% vs 100% in SHHF-TMAO. In vitro, exposure of LDH to HPS with or without TMAO did not affect protein structure. In conclusion, TMAO reduced mortality in SHHF, which was associated with diuretic, natriuretic and hypotensive effects. HPS and TMAO did not affect LDH protein structure.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all figures and tables.

Article and author information

Author details

  1. Marta Gawrys-Kopczynska

    Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Warsaw, Poland
    Competing interests
    The authors declare that no competing interests exist.
  2. Marek Konop

    Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Warsaw, Poland
    Competing interests
    The authors declare that no competing interests exist.
  3. Klaudia Maksymiuk

    Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Warsaw, Poland
    Competing interests
    The authors declare that no competing interests exist.
  4. Katarzyna Kraszewska

    Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Warsaw, Poland
    Competing interests
    The authors declare that no competing interests exist.
  5. Ladislav Derzsi

    Soft Condensed Matter, Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland
    Competing interests
    The authors declare that no competing interests exist.
  6. Krzysztof Sozanski

    Soft Condensed Matter, Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland
    Competing interests
    The authors declare that no competing interests exist.
  7. Robert Holyst

    Soft Condensed Matter, Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland
    Competing interests
    The authors declare that no competing interests exist.
  8. Marta Pilz

    Soft Condensed Matter, Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland
    Competing interests
    The authors declare that no competing interests exist.
  9. Emilia Samborowska

    Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland
    Competing interests
    The authors declare that no competing interests exist.
  10. Leszek Dobrowolski

    Department of Renal and Body Fluid Physiology, M Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
    Competing interests
    The authors declare that no competing interests exist.
  11. Kinga Jaworska

    Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Warsaw, Poland
    Competing interests
    The authors declare that no competing interests exist.
  12. Izabella Mogilnicka

    Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Warsaw, Poland
    Competing interests
    The authors declare that no competing interests exist.
  13. Marcin Ufnal

    Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Warsaw, Poland
    For correspondence
    mufnal@wum.edu.pl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0088-8284

Funding

Narodowe Centrum Nauki (2018/31/B/NZ5/00038.)

  • Marcin Ufnal

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The study was performed according to Directive 2010/63 EU on the protection of animals used for scientific purposes and approved by the Local Bioethical Committee in Warsaw (permission:100/2016 and 098/2019).

Reviewing Editor

  1. Arduino A Mangoni, Flinders Medical Centre, Australia

Version history

  1. Received: March 19, 2020
  2. Accepted: June 7, 2020
  3. Accepted Manuscript published: June 8, 2020 (version 1)
  4. Version of Record published: July 3, 2020 (version 2)

Copyright

© 2020, Gawrys-Kopczynska et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Marta Gawrys-Kopczynska
  2. Marek Konop
  3. Klaudia Maksymiuk
  4. Katarzyna Kraszewska
  5. Ladislav Derzsi
  6. Krzysztof Sozanski
  7. Robert Holyst
  8. Marta Pilz
  9. Emilia Samborowska
  10. Leszek Dobrowolski
  11. Kinga Jaworska
  12. Izabella Mogilnicka
  13. Marcin Ufnal
(2020)
TMAO, a seafood-derived molecule, produces diuresis and reduces mortality in heart failure rats
eLife 9:e57028.
https://doi.org/10.7554/eLife.57028

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    A retrospective cohort study utilizing payer-complete health insurance claims data from 8,239,790 patients with continuous medical and prescription insurance January 1, 2019 to June 30, 2020 was performed. The primary exposure of interest was use of any bisphosphonate from January 1, 2019 to February 29, 2020. Bisphosphonate users were identified as patients having at least one bisphosphonate claim during this period, who were then 1:1 propensity score-matched to bisphosphonate non-users by age, gender, insurance type, primary-care-provider visit in 2019, and comorbidity burden. Main outcomes of interest included: (a) any testing for SARS-CoV-2 infection; (b) COVID-19 diagnosis; and (c) hospitalization with a COVID-19 diagnosis between March 1, 2020 and June 30, 2020. Multiple sensitivity analyses were also performed to assess core study outcomes amongst more restrictive matches between BP users/non-users, as well as assessing the relationship between BP-use and other respiratory infections (pneumonia, acute bronchitis) both during the same study period as well as before the COVID outbreak.

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    Prior bisphosphonate-use was associated with dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations. Prospective clinical trials will be required to establish a causal role for bisphosphonate-use in COVID-19-related outcomes.

    Funding:

    This study was supported by NIH grants, AR068383 and AI155865, a grant from MassCPR (to UHvA) and a CRI Irvington postdoctoral fellowship, CRI2453 (to PH).