Gestational Paracetamol (Acetaminophen) Toxicity Induces Behavioral and Structural Brain Defects in Rats

Paracetamol is a well-known analgesic drug. Studies linked gestational paracetamol use to disorders like autism and attention-deficit/hyperactivity disorder. This study aimed to evaluate the role of prenatal paracetamol exposure in 1-month-old offspring rats. Sixteen pregnant albino rats were divided into four groups: group I received saline; group II received sodium valproate 600 mg/kg i.p. on embryonic day 13; group III received paracetamol 100 mg/kg i.p. daily from embryonic day 13 to 21; group IV received paracetamol 300 mg/kg i.p. on embryonic day 13. Offspring were assessed for behavioral test parameters. Animal brains underwent histopathological and immunohistochemical analysis for brain-derived neurotrophic factor (BDNF). Offspring in groups II (valproic acid) and IV (single paracetamol dose) showed differences in neurobehavioral test parameters, supported by cerebellar and hippocampal pathology. BDNF-stained cerebellum and hippocampus sections from the valproic group and the single paracetamol group revealed focal staining in granular cerebellar cells and pyramidal hippocampal cells. These findings indicate that prenatal exposure to high doses of paracetamol induces neurodevelopmental pathology. The safety of paracetamol use during pregnancy requires further evaluation.