Liver and Kidney Tissues Under Opioid Exposure: Rewriting and Old Story Through Proteomics and MALDI–MSI

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).