Influence of Indomethacin on Steroid Metabolism: Endocrine Disruption and Confounding Effects in Urinary Steroid Profiling of Anti-Doping Analyses
Anabolic androgenic steroids (AAS) are prohibited as doping substances in sports by the World Anti-Doping Agency. Concentrations and concentration ratios of endogenous AAS (steroid profile markers) in urine samples collected from athletes are used to detect their administration. Certain (non-prohibi...
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| Format: | Article |
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MDPI AG
2020-11-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/10/11/463 |
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| author | Anna Stoll Michele Iannone Giuseppina De Gregorio Francesco Molaioni Xavier de la Torre Francesco Botrè Maria Kristina Parr |
| author_facet | Anna Stoll Michele Iannone Giuseppina De Gregorio Francesco Molaioni Xavier de la Torre Francesco Botrè Maria Kristina Parr |
| author_sort | Anna Stoll |
| collection | DOAJ |
| description | Anabolic androgenic steroids (AAS) are prohibited as doping substances in sports by the World Anti-Doping Agency. Concentrations and concentration ratios of endogenous AAS (steroid profile markers) in urine samples collected from athletes are used to detect their administration. Certain (non-prohibited) drugs have been shown to influence the steroid profile and thereby sophisticate anti-doping analysis. It was shown in vitro that the non-steroidal anti-inflammatory drug (NSAID) indomethacin inhibits selected steroid-biotransformations catalyzed by the aldo-keto reductase (AKR) 1C3, which plays a key role in the endogenous steroid metabolism. Kinetic parameters for the indomethacin-mediated inhibition of the AKR1C3 catalyzed reduction in etiocholanolone were determined in vitro using two comparing methods. As NSAIDs are very frequently used (not only) by athletes, the inhibitory impact of indomethacin intake on the steroid metabolism was evaluated, and steroid profile alterations were detected in vivo (one male and one female volunteer). Significant differences between samples collected before, during or after the intake of indomethacin for selected steroid profile markers were observed. The presented results are of relevance for the interpretation of results from doping control analysis. Additionally, the administration of NSAIDs should be carefully reconsidered due to their potential as endocrine disruptors. |
| first_indexed | 2024-03-10T14:51:32Z |
| format | Article |
| id | doaj.art-1e67ab6dc1d1449f8a68bcc2644bcbb7 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T14:51:32Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-1e67ab6dc1d1449f8a68bcc2644bcbb72023-11-20T20:56:44ZengMDPI AGMetabolites2218-19892020-11-01101146310.3390/metabo10110463Influence of Indomethacin on Steroid Metabolism: Endocrine Disruption and Confounding Effects in Urinary Steroid Profiling of Anti-Doping AnalysesAnna Stoll0Michele Iannone1Giuseppina De Gregorio2Francesco Molaioni3Xavier de la Torre4Francesco Botrè5Maria Kristina Parr6Institute of Pharmacy (Pharmaceutical and Medical Chemistry), Freie Universität Berlin, 14195 Berlin, GermanyLaboratorio Antidoping Federazione Medico Sportiva Italiana, 00197 Rome, ItalyLaboratorio Antidoping Federazione Medico Sportiva Italiana, 00197 Rome, ItalyLaboratorio Antidoping Federazione Medico Sportiva Italiana, 00197 Rome, ItalyLaboratorio Antidoping Federazione Medico Sportiva Italiana, 00197 Rome, ItalyLaboratorio Antidoping Federazione Medico Sportiva Italiana, 00197 Rome, ItalyInstitute of Pharmacy (Pharmaceutical and Medical Chemistry), Freie Universität Berlin, 14195 Berlin, GermanyAnabolic androgenic steroids (AAS) are prohibited as doping substances in sports by the World Anti-Doping Agency. Concentrations and concentration ratios of endogenous AAS (steroid profile markers) in urine samples collected from athletes are used to detect their administration. Certain (non-prohibited) drugs have been shown to influence the steroid profile and thereby sophisticate anti-doping analysis. It was shown in vitro that the non-steroidal anti-inflammatory drug (NSAID) indomethacin inhibits selected steroid-biotransformations catalyzed by the aldo-keto reductase (AKR) 1C3, which plays a key role in the endogenous steroid metabolism. Kinetic parameters for the indomethacin-mediated inhibition of the AKR1C3 catalyzed reduction in etiocholanolone were determined in vitro using two comparing methods. As NSAIDs are very frequently used (not only) by athletes, the inhibitory impact of indomethacin intake on the steroid metabolism was evaluated, and steroid profile alterations were detected in vivo (one male and one female volunteer). Significant differences between samples collected before, during or after the intake of indomethacin for selected steroid profile markers were observed. The presented results are of relevance for the interpretation of results from doping control analysis. Additionally, the administration of NSAIDs should be carefully reconsidered due to their potential as endocrine disruptors.https://www.mdpi.com/2218-1989/10/11/463NSAIDinhibitiondopingaldo-keto reductasesendocrine disruption |
| spellingShingle | Anna Stoll Michele Iannone Giuseppina De Gregorio Francesco Molaioni Xavier de la Torre Francesco Botrè Maria Kristina Parr Influence of Indomethacin on Steroid Metabolism: Endocrine Disruption and Confounding Effects in Urinary Steroid Profiling of Anti-Doping Analyses Metabolites NSAID inhibition doping aldo-keto reductases endocrine disruption |
| title | Influence of Indomethacin on Steroid Metabolism: Endocrine Disruption and Confounding Effects in Urinary Steroid Profiling of Anti-Doping Analyses |
| title_full | Influence of Indomethacin on Steroid Metabolism: Endocrine Disruption and Confounding Effects in Urinary Steroid Profiling of Anti-Doping Analyses |
| title_fullStr | Influence of Indomethacin on Steroid Metabolism: Endocrine Disruption and Confounding Effects in Urinary Steroid Profiling of Anti-Doping Analyses |
| title_full_unstemmed | Influence of Indomethacin on Steroid Metabolism: Endocrine Disruption and Confounding Effects in Urinary Steroid Profiling of Anti-Doping Analyses |
| title_short | Influence of Indomethacin on Steroid Metabolism: Endocrine Disruption and Confounding Effects in Urinary Steroid Profiling of Anti-Doping Analyses |
| title_sort | influence of indomethacin on steroid metabolism endocrine disruption and confounding effects in urinary steroid profiling of anti doping analyses |
| topic | NSAID inhibition doping aldo-keto reductases endocrine disruption |
| url | https://www.mdpi.com/2218-1989/10/11/463 |
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