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

Background and aim 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.Experimental approach We established a murine model and systematically evaluated its toxic effects using blood biochemical, histopathological examination, and immunohistochemistry.Key findings 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.Conclusions 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.