Abstract
BackgroundOpioids 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.ResultsWe 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.ConclusionsOur 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.
Highlights
Opioids are the most effective drugs commonly prescribed to treat pain
We demonstrated increased levels of protein carbonylation in rat cortex and accumulation of TritonTM X-100 insoluble carbonyl-protein aggregates in blood plasma of animals treated with oxycodone, indicating a systemic degenerative process
Oxycodone increases protein carbonyl content in rat cortex To investigate whether chronic opioid administration increases the level of carbonyl-protein content in rat brain, we analyzed brain lysates of rats orally gavaged with 15 mg/kg of oxycodone every 24 h for 30 days
Summary
Opioids are a type of drugs that commonly prescribed to treat pain Due to their addictive nature, opioid pain relievers are second to marijuana, ahead of cocaine with respect to dependence. In 2010, a study investigating the effect of prescription opioids on brain structure of opioid dependent patients demonstrated the correlation between duration of drug use and alternations in brain functional connectivity, especially in regions responsible for impulse control, reward and motivation [2]. These changes included leukoencephalopathy, axon demyelination, and white matter lesions. The main methods to monitor neuronal degeneration in the brains of living people are the magnetic resonance imaging (MRI) and Positron Emission
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