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Gestational Paracetamol (Acetaminophen) Toxicity Induces Behavioral and Structural Brain Defects in Rats
Linah H Ali1, Hanaa A Khalaf2,3, Sameera S Hamed1
1Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
Insights
Prenatal exposure to high doses of paracetamol in rats may impact offspring neurodevelopment. This study suggests potential risks, highlighting the need for further evaluation of paracetamol safety during pregnancy.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Paracetamol (acetaminophen) is a widely used analgesic.
- Gestational paracetamol use has been tentatively linked to neurodevelopmental disorders in offspring.
- The precise impact of prenatal paracetamol exposure on offspring neurodevelopment requires further investigation.
Purpose of the Study:
- To investigate the effects of prenatal paracetamol exposure on neurobehavioral and neuropathological outcomes in 1-month-old rat offspring.
- To assess the role of brain-derived neurotrophic factor (BDNF) in paracetamol-induced neurodevelopmental changes.
Main Methods:
- Pregnant rats were administered saline, sodium valproate (positive control), or varying doses of paracetamol during critical developmental periods.
- Offspring were evaluated using neurobehavioral tests.
- Histopathological and immunohistochemical analyses were performed on offspring brains, focusing on the cerebellum and hippocampus, and assessing BDNF expression.
Main Results:
- Offspring exposed prenatally to a single high dose of paracetamol (group IV) and valproic acid (group II) exhibited significant alterations in neurobehavioral parameters.
- These behavioral changes were correlated with observed cerebellar and hippocampal pathology.
- Immunohistochemical analysis revealed altered BDNF staining patterns in the cerebellum and hippocampus of exposed offspring.
Conclusions:
- High-dose prenatal paracetamol exposure can induce neurodevelopmental pathology in rat offspring.
- The findings suggest that the safety of paracetamol use during pregnancy warrants continued scrutiny and further research.
- Altered BDNF expression may play a role in the observed neurodevelopmental effects.
Abstract:
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.
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