Opioid use affects antioxidant activity and purine metabolism: preliminary results
Opioid use affects antioxidant activity and purine metabolism: preliminary results
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DOI：
10.1002/hup.1068
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发表时间：
2009-12-01
影响因子：
1.7
通讯作者：
Kaddurah-Daouk, Rima
中科院分区：
文献类型：
--
作者：
Mannelli, Paolo;Patkar, Ashwin;Kaddurah-Daouk, Rima
目标 必须更多地了解有助于药物依赖性发展和表现的代谢和生化改变。实验性阿片类药物的施用会影响氧化应激的机制和指标，例如抗氧化剂化合物和嘌呤代谢。我们检查了阿片类药物依赖 (OD) 中神经递质相关通路的扰动。 方法 在这项初步研究中，我们使用靶向代谢组学平台，通过比较 OD 个体 (n = 14) 和非吸毒者 (n = 10) 来探索生化变化是否与 OD 相关。结果 接受短期美沙酮戒毒的 OD 患者表现出氧化还原活性的改变，如 较高的血浆α-和γ-生育酚水平以及GSH/GSSG 比率增加证实了这一点。 OD个体也改变了嘌呤代谢，表现出鸟嘌呤和黄嘌呤核苷浓度增加，鸟苷、次黄嘌呤、次黄嘌呤/黄嘌呤和黄嘌呤/黄嘌呤比率降低。除阿片类药物外，其他药物的使用与部分不同的生化变化相关。结论这是利用代谢组学进行的初步研究，显示 OD 中代谢途径的多种外周改变。进一步的研究应探索与激动剂和拮抗剂治疗相关的阿片类药物滥用、戒断和长期戒断状况的代谢特征，并研究阿片类物质和药物的生化特征。版权所有 (C) 2009 John Wiley & Sons, Ltd.
Objective More must be learned about metabolic and biochemical alterations that contribute to the development and expression of drug dependence. Experimental opioid administration influences mechanisms and indices of oxidative stress, such as antioxidant compounds and purine metabolism. We examined perturbations of neurotransmitter-related pathways in opioid dependence (OD).Methods In this preliminary study, we used a targeted metabolomics platform to explore whether biochemical changes were associated with OD by comparing OD individuals (n = 14) and non-drug users (n = 10).Results OD patients undergoing short-term methadone detoxification showed altered oxidation-reduction activity, as confirmed by higher plasma levels of alpha- and gamma-tocopherol and increased GSH/GSSG ratio. OD individuals had also altered purine metabolism, showing increased concentration of guanine and xanthosine, with decreased guanosine, hypoxanthine and hypoxanthine/xanthine and xanthine/xanthosine ratios. Other drug use in addition to opioids was associated with partly different biochemical changes.Conclusions This is a preliminary investigation using metabolomics and showing multiple peripheral alterations of metabolic pathways in OD. Further studies should explore the metabolic profile of conditions of opioid abuse, withdrawal and long-term abstinence in relation to agonist and antagonist treatment and investigate biochemical signatures of opioid substances and medications. Copyright (C) 2009 John Wiley & Sons, Ltd.