Department of Emergency Medicine, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, USA.
Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, USA.
BMC Neurosci. 2020 Jan 22;21(1):4. doi: 10.1186/s12868-020-0552-2.
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.
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.
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.
阿片类药物是最常被用来治疗疼痛的有效药物。由于其成瘾性,阿片类止痛药现在仅次于大麻,而可卡因则更依赖于依赖性。我们和其他研究表明,慢性阿片类药物给药可能会导致神经元变性,从而产生潜在的毒性作用。有人提出,蛋白质羰基化可能代表细胞变性的敏感生物标志物。为了评估长期使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,我们测量了 30 天每天 15mg/kg 羟考酮给药后大鼠大脑和血浆中的蛋白质羰基化水平。
与水治疗的动物相比,我们观察到在 30 天羟考酮治疗后大鼠大脑皮质中羰基化蛋白质的水平显著增加。此外,羟考酮治疗的大鼠在血浆中表现出不溶性羰基蛋白聚集体的积累。
我们的数据表明,检测血液中不溶性羰基蛋白聚集体的试验可以作为一种廉价且微创的方法,用于监测有慢性阿片类药物使用史的患者的神经元变性。这些方法可用于检测其他药物的毒性副作用,并监测衰老和神经退行性疾病的进展。