Inhaled microcystin-LR may induce acute liver failure through hepatic congestion

Area of Science:

• Environmental Health
• Toxicology
• Public Health

Background:

• Climate change is increasing cyanobacteria blooms, leading to greater environmental exposure to microcystin-leucine-arginine (MC-LR).
• MC-LR is a potent toxin produced by cyanobacteria, posing a significant public health concern due to potential human exposure routes.

Purpose of the Study:

• To investigate the health effects and toxicity of inhaled microcystin-leucine-arginine (MC-LR) in a mouse model.
• To determine the potential for MC-LR translocation across the airway epithelium and its target organs.
• To establish a potential acceptable inhalation dose for MC-LR.

Main Methods:

• MC-LR was administered intranasally to male and female mice at various doses.
• Mice were monitored for mortality, clinical signs, and pathological changes.
• Pulmonary and hepatic tissues were analyzed for inflammation, MC-LR presence, and gene expression changes.
• A 3D human airway model was used to assess MC-LR translocation.

Main Results:

• Inhaled MC-LR caused dose-dependent mortality in mice, with females showing higher sensitivity.
• Severe hepatic congestion and liver toxicity were observed in affected mice.
• MC-LR was detected in liver tissues within 2 hours post-exposure and translocated across airway epithelium.
• Significant changes in liver gene expression, including upregulation of ATF3 and NR4A1, and downregulation of miR-122, were noted.

Conclusions:

• Inhaled MC-LR induces liver-specific toxicity primarily through hepatic congestion.
• The acceptable inhalation dose of MC-LR is suggested to be below 10 μg/kg.
• Further research on chronic exposure to environmental concentrations of MC-LR is warranted due to increasing water pollution.