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

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ORIGINAL ARTICLE

Distinct lipid signatures are identified in the plasma of rats with chronic inflammation induced by estradiol benzoate and sex hormones Noriko Nakamura1   · Lisa M. Pence1 · Zhijun Cao1 · Richard D. Beger1 Received: 6 April 2020 / Accepted: 18 August 2020 © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2020

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. Keywords  Rats · Plasma · Lipid profiling · Estradiol · Testosterone · Chronic inflammation

1 Introduction

Disclaimer  The views expressed are those of the authors and do not represent the views of the U.S. Food and Drug Administration. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1130​6-020-01715​-w) contains supplementary material, which is available to authorized users. * Noriko Nakamura [email protected] 1



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

Prostatitis is inflammation of the prostate gland and is more likely to occur in people 45 years old and younger; older people are more likely to develop prostate cancer (Collin et al. 1998; Nickel 2011, 2012; Sfanos et al. 2018). Overall rate of prostatitis is 8.2% (2.2