Therapeutic concentration of morphine reduces oxidative stress in glioma cell line
Therapeutic concentration of morphine reduces oxidative stress in glioma cell line
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DOI：
10.1590/1414-431x20143697
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发表时间：
2014-04-01
影响因子：
2.3
通讯作者：
Crespo-López, M.E.
中科院分区：
文献类型：
--
作者：
Almeida, M.B.;Costa-Malaquias, A.;Crespo-López, M.E.
吗啡是一种有效的止痛阿片类药物，广泛用于疼痛治疗。在过去的十年里，全球消费增长了4倍多。然而，吗啡诱导的分子机制并不完全清楚。因此，越来越多的文献表明，止痛作用还有其他作用。以前关于吗啡和氧化应激的研究是有争议的，使用的浓度超出了临床实践的范围。因此，在这项研究中，我们假设治疗浓度的吗啡(1 MM)在传统的氧化应激模型中显示出保护作用。我们将C6胶质瘤细胞系暴露于过氧化氢(H_2O_2)和/或吗啡24小时，并评估细胞存活率、脂质过氧化和巯基水平(细胞氧化还原状态的指标)。吗啡不能阻止过氧化氢引起的细胞存活率下降，但部分阻止了0.0025%的过氧化氢引起的脂质过氧化(该浓度允许细胞存活率超过90%)。有趣的是，这种阿片类药物并没有改变暴露于0.0025%H_2O_2所产生的增加的巯基水平，这开启了另一种分子机制(直接清除活性或抑制NAPH氧化酶)可能解释在脂质过氧化检测中登记的保护作用的可能性。我们的结果首次证明，通常剂量的吗啡可能有助于将神经胶质细胞的氧化应激降至最低。这项研究支持使用与临床实践中使用的浓度相似的浓度的重要性，以便在实验模型和临床环境之间更好地接近。
Morphine is a potent analgesic opioid used extensively for pain treatment. During the last decade, global consumption grew more than 4-fold. However, molecular mechanisms elicited by morphine are not totally understood. Thus, a growing literature indicates that there are additional actions to the analgesic effect. Previous studies about morphine and oxidative stress are controversial and used concentrations outside the range of clinical practice. Therefore, in this study, we hypothesized that a therapeutic concentration of morphine (1 mM) would show a protective effect in a traditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogen peroxide (H2O2) and/or morphine for 24 h and evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of the redox state of the cell). Morphine did not prevent the decrease in cell viability provoked by H2O2 but partially prevented lipid peroxidation caused by 0.0025% H2O2 (a concentration allowing more than 90% cell viability). Interestingly, this opioid did not alter the increased levels of sulfhydryl groups produced by exposure to 0.0025% H2O2, opening the possibility that alternative molecular mechanisms (a direct scavenging activity or the inhibition of NAPDH oxidase) may explain the protective effect registered in the lipid peroxidation assay. Our results demonstrate, for the first time, that morphine in usual analgesic doses may contribute to minimizing oxidative stress in cells of glial origin. This study supports the importance of employing concentrations similar to those used in clinical practice for a better approximation between experimental models and the clinical setting.