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Gestational Paracetamol Toxicity Induces Behavioral and Structural Brain Defects in Rats with Direct Effect

Linah Ali, Hanaa Khalaf, Sameera Shaaban, Ahmed Mohamed Helaly, Aya Elsayed Maghrabia, Amal A. El Bakary

Preprints.org, 2025

Abstract

Paracetamol is a well-known analgesic drug. Studies linked the gestational use of paracetamol with the pathogenesis of disorders like autism and attention defect hyperactivity disorders. This work aims to evaluate the role of prenatal exposure of paracetamol on 1-month-old rats offspring. Sixteen pregnant albino rats were used in this study and divided into four groups including group I received distilled water, group II received sodium valproate 600 mg/Kg i.p at 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 at embryonic day 13. Offspring were examined for behavior test parameters. Animal brains were examined for histopathology and immunohistochemistry for brain-derived neurotrophic factor (BDNF). Offspring of group II (valproic acid) and group IV single paracetamol showed a difference in the neurobehavioral test parameters supported by cerebellar and hippocampus pathology. BDNF stained sections of the cerebellum and the hippocampus of the offspring of the valproic group. The single paracetamol group expressed focal staining for the granular cerebellar cells and the pyramidal hippocampal ones. These findings concluded that prenatal exposure to high paracetamol dose induced neurodevelopmental pathology. Paracetamol use in pregnancy needs further evaluation.

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