Neonatal Benzo[a]pyrene Exposure Induces Oxidative Stress and DNA Damage Causing Neurobehavioural Changes during the Early Adolescence Period in Rats.
Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) by ingestion of contaminated food and water. Prenatal exposure to benzo[a]pyrene (B[a]P) like PAHs through the placental barrier and neonatal exposure by breast milk and the environment may affect early brain development. In the present study, single intracisternal administration of B[a]P (0.2 and 2.0 µg/kg body weight) to male Wistar rat pups at postnatal day 5 (PND5) was carried out to study its specific effect on neonatal brain development and its consequences at PND30. B[a]P administration showed a significant increase in exploratory and anxiolytic-like behaviour with elevated hippocampal lipid peroxidation and protein oxidation at PND30. Further, DNA damage was estimated in vitro (Neuro2a and C6 cell lines) by the comet assay, and oxidative DNA damage of hippocampal sections was measured in vivo following exposure to B[a]P. DNA strand breaks (single and double) significantly increased due to B[a]P at PND30 in hippocampal neurons and increased the nuclear tail moment in Neuro2a cells. Hippocampal 8-oxo-2'-deoxyguanosine production was significantly elevated showing expression of more TUNEL-positive cells in both doses of B[a]P. Histological studies also revealed a significant reduction in mean area and perimeter of hippocampal neurons in rats treated with B[a]P 2.0 μg/kg, when compared to naïve and control rats. B[a]P significantly increased anxiolytic-like behaviour and oxidative DNA damage in the hippocampus causing apoptosis that may lead to neurodegeneration in adolescence. The findings of the present study address the potential role of B[a]P in inducing oxidative stress-mediated neurodegeneration in the hippocampus through oxidative DNA damage in the early adolescence period of rats.
Neurobiology Laboratory, Department of Zoology, School of Life Sciences, Ravenshaw University, Cuttack, India.
Bhupesh
B
Patel
Saroj Kumar
SK
Das
Manorama
M
Patri
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D004249:DNA Damage; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development; D015227:Lipid Peroxidation / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*
D001564:Benzo(a)pyrene