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Liver and Kidney Tissues Under Opioid Exposure: Rewriting and Old Story Through Proteomics and MALDI-MSI
Malgorzata Hopcias1, Paulina Kret1, Jolanta H Kotlinska2
1Department of Analytical Chemistry and Biochemistry, AGH University of Krakow, Mickiewicza 30 Avenue, 30-059 Krakow, Poland.
Abstract:
A proteomic analysis of rat liver and kidney was performed following exposure to morphine (10 mg/kg, 10 days) versus untreated controls. Our data revealed alterations in numerous protein expression. Differences were observed in pro- and antiapoptotic signaling, oxidative stress response, transport mechanisms, nucleic acid metabolism, and regulators of alternative splicing, among others. Liver tissue exhibited primarily adaptive changes, including upregulation of metabolic enzymes and subtle markers of oxidative stress. In contrast, the kidneys displayed a broader spectrum of proteomic alterations, affecting a wider array of functional pathways, suggesting that this organ may be more susceptible to morphine-induced toxicity or that of its metabolites. We employed also MALDI-MSI to examine lipidomic alterations: while no significant changes were detected in liver tissue, important lipidomic alterations were observed in the kidneys, further supporting their increased vulnerability to morphine exposure. Our results should be regarded as preliminary; however, they highlight a promising direction for identifying early stage protein markers of toxicity using proteomic approaches. Monitoring such markers could prove valuable in multidrug therapies, particularly for patients with a history of hepatic or renal impairment, contributing to the development of safer therapeutic strategies. Data are available via ProteomeXchange under the identifiers: PXD067999 (DDA) and PXD068084 (DIA).
Insights
Morphine exposure alters protein and lipid profiles in rat kidneys more than livers. These findings suggest kidneys may be more vulnerable to morphine toxicity, offering potential early markers for safer drug therapies.
Area of Science:
- Proteomics and Lipidomics
- Toxicology
- Pharmacology
Background:
- Morphine is widely used for pain management.
- Understanding morphine's organ-specific effects is crucial for patient safety.
- Proteomic and lipidomic analyses offer insights into cellular responses to drugs.
Purpose of the Study:
- To investigate the proteomic and lipidomic changes in rat liver and kidney following morphine exposure.
- To identify potential organ-specific toxicity markers of morphine.
Main Methods:
- Proteomic analysis of rat liver and kidney tissues after 10 days of morphine administration (10 mg/kg).
- Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) for lipidomic analysis.
- Comparison of protein and lipid expression profiles between treated and control groups.
Main Results:
- Significant alterations in protein expression were observed in both liver and kidney, affecting apoptosis, oxidative stress, metabolism, and splicing.
- Kidney tissues showed a broader range of proteomic alterations compared to liver tissues.
- While liver lipid profiles remained unchanged, kidneys exhibited significant lipidomic alterations, indicating increased vulnerability.
Conclusions:
- Rat kidneys appear more susceptible to morphine-induced toxicity or metabolite effects than the liver.
- Proteomic and lipidomic approaches can identify early-stage toxicity markers for morphine.
- These findings could aid in developing safer therapeutic strategies, especially for patients with pre-existing renal or hepatic conditions.
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