Toxic effects in mice exposed to mushroom toxin ibotenic acid: a dose- and time-dependent study

Ibotenic acid, a neurotoxin found in poisonous mushrooms, induces neurotoxic effects; however, comprehensive in vivo toxicity data remain scarce. This study aimed to systematically evaluate the toxic effects of ibotenic acid using a murine model.
We established a murine model and systematically evaluated its toxic effects using blood biochemical, histopathological examination, and immunohistochemistry.
Ibotenic acid exhibited dose- and time-dependent toxicity. At 16 mg/kg, mice exhibited reduced activity, somnolence, and tremors, accompanied by transient changes in glucose, urea, and calcium levels that normalized within 240 min. No mortality was observed at this dose. In contrast, 33 mg/kg induced severe toxicity within 75 min, marked by significant abnormalities in ALT, UA, CK, GLU, K, and Ca levels, as well as mortality. Histopathology revealed no overt tissue damage, but showed upregulated c-fos expression at an early stage. High-dose exposure caused a significant reduction of Nissl bodies within the cerebral cortex and hippocampus. Neither neuronal density nor the number of astrocytes and microglia varied significantly across dose groups.
This study systematically elucidates the toxic effects of ibotenic acid, demonstrating its dose- and time-dependent impact, revealing that short-term exposure can cause behavioral abnormalities, biochemical disorders, and neuronal damage.
This study provides the first systematic in vivo evidence of the dose- and time-dependent neurotoxicity of ibotenic acid, offering valuable insights into its early behavioral, biochemical, and neuronal effects. Utilizing a murine model, we identified key toxicity markers, including early c-fos activation and a reduction in Nissl bodies, which serve as indicators of neuronal injury. These findings enhance the toxicological framework of mushroom poisoning and provide a theoretical basis for mechanistic studies and clinical interventions regarding neurotoxic mushroom poisoning, particularly in regions with a high incidence of such exposures.