Almeida M B, Costa-Malaquias A, Nascimento J L M, Oliveira K R, Herculano A M, Crespo-López M E
Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
Laboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
Braz J Med Biol Res. 2014 May;47(5):398-402. doi: 10.1590/1414-431x20143697. Epub 2014 May 2.
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 μM) 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.
吗啡是一种强效镇痛阿片类药物，广泛用于疼痛治疗。在过去十年中，全球消费量增长了四倍多。然而，吗啡引发的分子机制尚未完全明确。因此，越来越多的文献表明，除镇痛作用外还有其他作用。先前关于吗啡与氧化应激的研究存在争议，且使用的浓度超出了临床实践范围。所以，在本研究中，我们假设治疗浓度的吗啡（1 μM）在传统氧化应激模型中会显示出保护作用。我们将C6胶质瘤细胞系暴露于过氧化氢（H2O2）和/或吗啡中24小时，并评估细胞活力、脂质过氧化以及巯基水平（细胞氧化还原状态的指标）。吗啡未能阻止H2O2引起的细胞活力下降，但部分阻止了0.0025% H2O2（一种能使细胞活力超过90%的浓度）所致的脂质过氧化。有趣的是，这种阿片类药物并未改变暴露于0.0025% H2O2所产生的升高的巯基水平，这表明可能存在其他分子机制（直接清除活性或抑制NAPDH氧化酶）来解释脂质过氧化实验中观察到的保护作用。我们的结果首次证明，常用镇痛剂量的吗啡可能有助于使神经胶质来源细胞中的氧化应激降至最低。本研究支持了采用与临床实践中相似浓度的重要性，以便实验模型与临床情况能更好地契合。
