Neonatal Benzo[a]pyrene Exposure Induces Oxidative Stress and DNA Damage Causing Neurobehavioural Changes during the Early Adolescence Period in Rats

Abstract

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.

Modulatory Effects of Silymarin on Benzo[a]pyrene-Induced Hepatotoxicity

“…B[a]P is a group I carcinogen that is widely produced in cigarette smoke, charbroiled food, and other sources. It activates several types of cancer, mainly by causing DNA damage through BPDE-DNA adduct and ROS formation [41,42]. Unfortunately, we are constantly exposed to low-doses of B[a]P, which induces cancer in the body through its conversion to the BPDE metabolite [43,44].…”

Integrated Hypoxia Signaling and Oxidative Stress in Developmental Neurotoxicity of Benzo[a]Pyrene in Zebrafish Embryos

“…Exposure to B[a]P is known to play a role in lung carcinogenesis induced by tissue inflammation [ 70 , 71 ]. In current years, the potential neurotoxicity of B[a]P inducing oxidative stress-mediated neurotoxicity and causing behavioral alterations and oxidative stress in animal models was reported [ 72 , 73 , 74 ]. B[a]P can reach the encephalic central nervous tissues by crossing the blood–brain barrier [ 75 , 76 , 77 ]; this leads to increase nervous oxidative stress in the nervous system which in turn resulting in behavioral changes and alterations to the expression of antioxidant enzymes (e.g., superoxide dismutase, catalase and glutathione peroxidase and cellular lipid peroxidation [ 77 , 78 ].…”

Neuropeptide Y Expression Confers Benzo[a]pyrene Induced DNA Damage and Microtubule Disruption in Human Neuroblastoma SH-SY5Y Cells

“…The result also showed differentiated SH-SY5Y cells respond differently to toxicants like B[a]P in higher and lower doses with different cell morphology. The present findings addresses the augmented expression of NPY in rat brain following exposure to B[a]P and its correlation with the orexigenic effects depending on the antioxidant activity [15,8,37].…”

“…Benzo[a]pyrene (B[a]P), a prototype of PAH is well known for its carcinogenic or mutagenic role [3,4], however in past decades, its neurotoxic potential is also well documented [5,6,7]. The neurotoxic potential of B[a]P is mainly achieved through neuromorphological alteration, cell cycle arrest, oxidative DNA damage, etc [8,9,10].…”