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The Long-Lasting Rodenticide Brodifacoum Induces Neuropathology in Adult Male Rats
Sergey Kalinin1, Natalia Marangoni1, Katarzyna Kowal1
1Department of Anesthesiology, University of Illinois, Chicago, Illinois 60612.
Toxicological Sciences : an Official Journal of the Society of Toxicology
|September 15, 2017
Summary
Superwarfarins like brodifacoum cause neuroinflammation and neuronal damage in rodents due to long-term tissue accumulation. These neurological effects persist even after initial toxicity concerns are addressed.
Area of Science:
- Toxicology
- Neuroscience
- Pharmacology
Background:
- Superwarfarins are potent, long-lasting rodenticides.
- Their chronic effects, particularly neurological, are not well understood.
- Brodifacoum (BDF) is a widely used superwarfarin with a long biological half-life.
Purpose of the Study:
- To characterize the neurological effects of brodifacoum (BDF) in adult rats.
- To investigate the accumulation and persistence of BDF in the central nervous system.
- To identify molecular pathways affected by BDF exposure.
Main Methods:
- Determined acute oral lethal dose of BDF in Sprague Dawley rats.
- Measured BDF tissue levels and assessed neuroinflammation and neuronal damage via immunocytochemistry and staining.
- Conducted proteomic analysis of rat cerebellar lysates and in vitro studies on primary neurons and astrocytes.
Main Results:
- BDF accumulated in tissues, including the CNS, with delayed clearance.
- Increased astrocyte and microglial activation, protein carbonylation, and neuronal damage were observed.
- Proteomic analysis revealed alterations in 667 proteins, impacting cell metabolism, mitochondrial function, and RNA handling; BDF suppressed protein synthesis in astrocytes.
Conclusions:
- Chronic superwarfarin accumulation leads to neuroinflammation and neuropathology in rodents.
- Delayed neurological sequelae may not be mitigated by standard toxicity reduction methods.
- Further research is needed to understand the long-term neurological impact of superwarfarin exposure.
