Effects of Long-Acting Anticoagulant Rodenticides on Rabbit Plasma Extracellular Vesicles

Area of Science:

• Environmental Toxicology
• Cellular Biology
• Biochemistry

Background:

• Extracellular vesicles (EVs) are crucial for intercellular communication and can transport substances across biological barriers, including the blood-brain barrier.
• Environmental toxicants can alter EV production and composition, impacting their physiological roles.
• Long-acting anticoagulant rodenticides (LAARs) pose a public health risk due to their persistence and potential toxicity.

Purpose of the Study:

• To investigate the impact of LAARs on plasma EV dynamics in rabbits.
• To determine if cholestyramine (CSA) affects LAAR-induced changes in EVs.
• To assess the association of LAARs with EVs and the functional consequences of EV alterations.

Main Methods:

• Plasma EVs were isolated from rabbits exposed to a mixture of three potent LAARs (brodifacoum, difenacoum, bromadiolone) using polymer-based precipitation.
• Nanoparticle tracking analysis (NTA) was used to quantify EV concentration and size distribution.
• Mass spectrometry identified LAARs associated with EVs, and their effects on microglial cells were assessed.

Main Results:

• LAAR exposure led to a time-dependent decrease in EV concentration and altered EV size distribution.
• Co-administration of CSA reversed some LAAR-induced EV alterations.
• All three LAARs were detected in isolated EVs, and CSA reduced their levels; EVs from LAAR-treated rabbits induced microglial cell death.

Conclusions:

• LAARs significantly influence the concentration and size of circulating EVs.
• EVs may serve as a mechanism for transporting LAARs throughout the body, contributing to their toxicity.
• CSA demonstrates potential in mitigating LAAR effects on EVs and possibly reducing systemic toxicant distribution.