Analysis of Elevated Levels of Nandrolone Decanoate Induced Cytochrome- P450 Alterations in Mice.

Drug metabolism letters Pub Date : 2017-01-01 DOI:10.2174/1872312811666171114145535

Parmita Chowdhury, Rita Mahanta

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Abstract

Background: Frequent recreational use of Anabolic Androgenic Steroids (AAS) is an instance of substance abuse which mimics the status of a natural hormone and upon prolonged exposure may lead to adverse drug reactions. These adverse drug reactions proceed in a manner so as to alter the normal metabolism of an enzyme mediated pathway such as the Cytochrome P450 (CYP) family of enzymes.

Objective: The present study was conducted to investigate the impact of overuse of Nandrolone Decanoate (ND), an AAS, upon CYP enzyme activity and a CYP gene, belonging to CYP1 family.

Methods: The study was carried out using normal and ND treated male albino mice. Genetic analysis was conducted using normalized and treated cDNA and reverse transcriptase polymerase chain reaction based assays. For enzyme assay, 0.1ml of 25 mg ND was administered to the animals twice a week for a period of 90 days. Genetic analysis was carried out with the same dose but administered for a period of 360 days.

Results: CYP enzyme activity increased significantly (p<0.01) in the ND treated group of animals compared to that in the normal group. However, no noticeable alteration was observed at the molecular level.

Conclusion: From the present study it could be inferred that, at elevated doses, ND has the potential to alter hepatic CYP enzyme activity without any modification in the CYP gene. This could be due to a possible adaptive response of the living system to such drugs.

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十酸诺龙高水平诱导小鼠细胞色素P450改变的分析。

背景:频繁的娱乐性使用合成代谢雄激素类固醇(AAS)是一种药物滥用的例子，它模仿天然激素的状态，长时间暴露可能导致药物不良反应。这些药物不良反应以某种方式进行，从而改变酶介导途径的正常代谢，如细胞色素P450 (CYP)酶家族。目的:探讨过量使用醋酸诺龙(ND)对CYP酶活性及CYP1家族CYP基因的影响。方法:以正常和ND治疗的雄性白化小鼠为研究对象。采用归一化和处理过的cDNA和逆转录聚合酶链式反应进行遗传分析。酶测定，每周两次给药0.1ml 25 mg ND，连续90天。遗传分析以相同剂量进行，但给药期为360天。结果:CYP酶活性显著增加(p结论:从本研究可以推断，在高剂量下，ND有可能改变肝脏CYP酶活性，而不改变CYP基因。这可能是由于生命系统对这些药物的一种可能的适应性反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug metabolism letters Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

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期刊介绍： Drug Metabolism Letters publishes letters and research articles on major advances in all areas of drug metabolism and disposition. The emphasis is on publishing quality papers very rapidly by taking full advantage of the Internet technology both for the submission and review of manuscripts. The journal covers the following areas: In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites.