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Metabolomics analysis of liver reveals profile disruption in bovines upon steroid treatment

ABSTRACT: INTRODUCTION: The surveillance of illegal anabolic practices in bovine meat production is necessary to guarantee consumers’ health. Screening strategies based on the recognition of indirect biological effects are considered by the community as promising tools to overcome some limitations of classical analytical methods and might therefore concur to ensure safer food for the consumer.
OBJECTIVES: The present work aims at characterizing the metabolic profile induced in liver by administration of anabolic steroids, and at identifying potential disturbances in the hepatic metabolism.
METHODS: A total of 32 liver samples, 16 from untreated bulls and 16 from bulls treated with an ear implant (Revalor-XS®) containing trenbolone acetate (200 mg) and ß-estradiol (40 mg), were analyzed following a LC–MS-based metabolomic analysis combining RP and HILIC chromatographic separations. Different multivariate statistical tools were applied to the datasets to select common metabolites that may be considered as potential markers based on their significant changes in concentrations after administration of sexual steroids.
RESULTS:Eight candidate markers were identified. Moreover, a subset of four markers was also validated by a different laboratory that performed the same analysis using an independent instrumental and elaboration platform, confirming the robustness of the results achieved.
CONCLUSION: This study was performed mimicking experimental conditions that may be used during a potential misuse practice. It is promising in the objective of setting up an analytical strategy to highlight sexual steroids abuse in livestock animals.

INSTRUMENT(S): Q-Exactive (Thermo Scientific)

SUBMITTER: Roberto Stella

PROVIDER: MTBLS436 | MetaboLights | 2018-05-08

REPOSITORIES: MetaboLights

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Project description:Commensal microbes are exposed to enterohepatically circulated steroids such as bile acids and hormones in the gastrointestinal, vaginal, and urinary tracts. Since commensal microbes are exposed to these molecules exclusively in association with their host, we hypothesized that they may serve as effectors to identify and characterize genetic pathways involved in the commensal-host relationship. Host specific and some ingested steroids (phytoestrogens) are enterohepatically circulated through the lumen of the small intestine. Bile acid steroids are present at high concentrations, approximating 4 to 20 mM in the duodenum, and are released in bile from the common bile duct. Steroid hormones are secreted in bile at levels approximating 6 to 13 mg per day once conjugated to glucuronide or sulfate by the liver. Re-absorption of steroids by the terminal ileum is an incomplete process: for example, 200 to 600 mg of bile acid steroids per day in humans escape to the colon where complex microbial populations exist. We have shown that steroid hormones estradiol, progesterone, and hydrocortisone serve as strong substrates for the major RND- and MFS-type (except hydrocortisone) tripartite multidrug efflux systems, AcrAB-TolC and EmrAB-TolC respectively, even though such molecules fail to demonstrate antimicrobial properties in this bacterial background (Elkins and Mullis [2006] J. Bacteriol. 188:1191-1195). Although bile acids are subject to efflux, they are also known to directly interact with intracellular global regulators such as MarR (Prouty et al. [2004] Microbiol. 150:775-783) and Rob (Rosenberg et al., [2003] Mol. Microbiol. 48:1609-1619) consequently altering antimicrobial and bile resistance profiles. In our present study, whole-genome DNA microarrays of E. coli were used to determine what general effect steroids, both bile acid and hormones, may have on the transcriptome in relation to the human commensal environment. Keywords: Comparative Chemical Class Treatment

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Metabolomics analysis of liver reveals profile disruption in bovines upon steroid treatment

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