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Distinct lipid signatures are identified in the plasma of rats with chronic inflammation induced by estradiol benzoate and sex hormones

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Abstract

Introduction

Prostatitis is likely to occur in younger or middle-aged men, while prostate cancer is likely to occur in older men. Although amino acids and lipids as biomarkers of prostate cancer have been examined using prostate cancer cell lines/tissues, no previous studies have evaluated amino acids or lipids as potential chronic prostatitis biomarkers.

Objectives

The study’s aim was to identify amino acids and lipids that could serve as potential biomarkers of chronic prostatitis.

Methods

We profiled the amino acids and lipids found in plasma from rats collected in a previous study. In brief, a total of 148 Sprague–Dawley rats (offspring) were dosed with estradiol benzoate (EB) on postnatal days (PNDs) 1, 3 and 5, and subsequently dosed with testosterone (T)/estradiol (E) tubes via subcutaneous implants from PND 90 to 200. Plasma was collected on PNDs 30, 90, 100, 145 and 200. Analysis was conducted with a Xevo TQ-S triple-quadrupole mass spectrometer using a Biocrates AbsoluteIDQ p180 kit.

Results

Plasma acylcarnitines [(C2, C16:1, C18, C18:1, C18:1-OH, and C18:2)], glycerophospholipids (lysophosphatidylcholine-acyl, -di-acyl, and -di-acyl acyl-alkyl) and sphingomyelins [SM (OH) C16:1, SM C18:0, SM C18:1, and SM C20:2] significantly increased on PND 145, when chronic inflammation was observed in the dorsolateral prostate of rats dosed with EB, T, and E. No statistical significances of amino acid levels were observed in the EB + T + E group on PND 145.

Conclusion

Exposure to EB, T, and E altered lipid levels in rat plasma with chronic prostate inflammation. These findings suggest that the identified lipids may be predictive chronic prostatitis biomarkers. The results require confirmation through additional nonclinical and human studies.

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Data availability

The data will be deposited at Metabolights once the manuscript is accepted.

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Acknowledgements

The authors thank Drs. Laura Schnackenberg and Pierre Alusta for their suggestions on the manuscript, and Dr. John K. Leighton (CDER) for his suggestions on this project proposal. The author (N.N.) thanks Mr. Ralph Patton and Ms. Kristie Voris, TPA, for plasma preparation, Ms. Sara Lewis for manuscript editing, and Ms. Patricia Shores and Ms. Kathy Carroll for preparing the cage cards.

Funding

This study was funded by NCTR/FDA (E0759701).

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Authors and Affiliations

  1. Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA

    Noriko Nakamura, Lisa M. Pence, Zhijun Cao & Richard D. Beger

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  1. Noriko Nakamura
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  2. Lisa M. Pence
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  3. Zhijun Cao
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Contributions

NN conceived of the presented idea and experimental design. NN wrote the manuscript and finalized the manuscript, incorporating all of the co-authors’ comments. LMP performed the metabolomic analysis, analyzed data, and assisted with manuscript preparation. ZC performed the statistical analysis and provided Figures. RDB suggested the appropriate metabolomics analysis method. LMP, ZC, and RDB provided suggestions.

Corresponding author

Correspondence to Noriko Nakamura.

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The authors declare no conflicts of interest.

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All applicable guidelines set by the National Research Council’s “Guide for the Care and Use of Laboratory Animals” and the NCTR Institutional Animal Care and Use Committee were followed.

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This study used animals and didn’t use any samples from humans. This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. We have read and understood your journal’s policies, and we believe that neither this manuscript nor this study violates any of those policies.

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Nakamura, N., Pence, L.M., Cao, Z. et al. Distinct lipid signatures are identified in the plasma of rats with chronic inflammation induced by estradiol benzoate and sex hormones. Metabolomics 16, 95 (2020). https://doi.org/10.1007/s11306-020-01715-w

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