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首页> 美国卫生研究院文献>Metabolites >Influence of Indomethacin on Steroid Metabolism: Endocrine Disruption and Confounding Effects in Urinary Steroid Profiling of Anti-Doping Analyses
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Influence of Indomethacin on Steroid Metabolism: Endocrine Disruption and Confounding Effects in Urinary Steroid Profiling of Anti-Doping Analyses

机译：吲哚美辛对类固醇代谢的影响：内分泌破坏抗掺杂分析中的泌尿原素剖析中的混淆效应

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摘要

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.
机译：合成代谢雄激素类固醇（AAS）被世界反兴奋剂机构作为运动中的掺杂物质。使用运动员收集的尿液样本中内源AAS（类固醇型材标记物）的浓度和浓度比用于检测其给药。已经证明某些（非禁止的）药物影响类固醇型材，从而影响抗掺杂分析。它显示在体外，非甾体抗炎药（NSAID）吲哚美辛抑制由Aldo-Keto还原酶（AKR）1C3催化的选定类固醇生物转化，其在内源性类固醇代谢中起着关键作用。使用两种比较方法在体外测定体外测定吲哚美辛介导的AkR1C3催化抑制的AKR1C3催化抑制的动力学参数。随着NSAID的经常使用（不仅）通过运动员（不仅），评估了吲哚美辛进气对类固醇代谢的抑制作用，并且在体内（一名男性和一名女性志愿者）中检测到类固醇简介改变。观察到在摄入吲哚美辛的吲哚美辛以期间，期间或之后所收集的样品之间的显着差异。所提出的结果与掺杂对照分析的结果的解释有关。此外，由于其作为内分泌破坏者的潜力，应小心重新考虑NSAID的给药。

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