Background Opioids are the most effective drugs commonly prescribed to treat pain. Due to their addictive nature, opioid pain relievers are now second to marijuana, ahead of cocaine with respect to dependence. Ours and other studies suggest potential toxic effects of chronic opioid administration leading to neuronal degeneration. It has been suggested that protein carbonylation may represent a sensitive biomarker of cellular degeneration. To evaluate whether prolonged oxycodone administration is associated with accumulation of protein aggregates that may contribute to neuronal degeneration we measured protein carbonylation levels in brain and also in blood plasma of rats after 30-days of 15 mg/kg daily oxycodone administration. Results We observed a significant increase in the level of carbonylated proteins in rat brain cortex after 30-days of oxycodone treatment compare to that in water treated animals. Also, oxycodone treated rats demonstrated accumulation of insoluble carbonyl-protein aggregates in blood plasma. Conclusions Our data suggests that tests detecting insoluble carbonyl-protein aggregates in blood may serve as an inexpensive and minimally invasive method to monitor neuronal degeneration in patients with a history of chronic opioid use. Such methods could be used to detect toxic side effects of other medications and monitor progression of aging and neurodegenerative diseases.

中文翻译：

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慢性羟考酮治疗后雌性大鼠脑和血液中羰基蛋白含量增加

背景 阿片类药物是通常用于治疗疼痛的最有效药物。由于它们的成瘾性，阿片类止痛药现在仅次于大麻，在依赖方面领先于可卡因。我们和其他研究表明，长期服用阿片类药物会导致神经元变性的潜在毒性作用。有人提出蛋白质羰基化可能代表细胞退化的敏感生物标志物。为了评估长期服用羟考酮是否与可能导致神经元变性的蛋白质聚集体的积累有关，我们在每天服用 15 mg/kg 羟考酮 30 天后测量了大鼠大脑和血浆中的蛋白质羰基化水平。结果我们观察到，与水处理动物相比，羟考酮处理 30 天后大鼠大脑皮层中羰基化蛋白的水平显着增加。此外，羟考酮治疗的大鼠显示血浆中不溶性羰基蛋白聚集体的积累。结论 我们的数据表明，检测血液中不溶性羰基蛋白聚集体的测试可以作为一种廉价且微创的方法来监测有慢性阿片类药物使用史的患者的神经元变性。此类方法可用于检测其他药物的毒副作用并监测衰老和神经退行性疾病的进展。结论 我们的数据表明，检测血液中不溶性羰基蛋白聚集体的测试可以作为一种廉价且微创的方法来监测有慢性阿片类药物使用史的患者的神经元变性。此类方法可用于检测其他药物的毒副作用并监测衰老和神经退行性疾病的进展。结论 我们的数据表明，检测血液中不溶性羰基蛋白聚集体的测试可以作为一种廉价且微创的方法来监测有慢性阿片类药物使用史的患者的神经元变性。此类方法可用于检测其他药物的毒副作用并监测衰老和神经退行性疾病的进展。