Benzo(a)pyrene‐induced acute neurotoxicity in the F‐344 rat: role of oxidative stress

Abstract

Given the link between neurotoxicity and exposure to pollutants, the potential behavioral neurotoxicity of benzo(a)pyrene [B(a)P] was investigated. Studies have established that B(a)P requires metabolic activation to highly reactive species to elicit many of its adverse effects. This study investigated the perturbation of nervous system function by correlating behavioral changes with the metabolism of B(a)P, antioxidant enzyme levels and lipid peroxidation in selected brain regions. The neurobehavioral effects of single oral doses of B(a)P (25-200 mg kg(-1) body weight) on motor activity were examined in male F-344 rats at 2, 4, 6, 12, 24, 48, 72 and 96 h post treatment. Parent B(a)P and metabolites were measured at the above mentioned time points by reverse phase HPLC. The activity of several antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and levels of malondialdehyde were determined at 6 and 96 h in both the striatum and hippocampus of B(a)P exposed rats. Suppression of motor activity (up to 70%) reached a maximum at 6 h, but was reversible at 96 h in all dose groups. The kinetics of disposition data show a strong link between B(a)P metabolism and the onset and duration of behavioral effects. Benzo(a)pyrene caused a 15-70% inhibition in the activity of superoxide dismutase and glutathione peroxidase and an enhancement in catalase and lipid peroxidation (up to 68%) in the striatum and hippocampus at 6 and 96 h post treatment, respectively. These findings suggest that B(a)P-induced acute neurobehavioral toxicity may occur through oxidative stress due to inhibition of the brain antioxidant scavenging system.

Association of selected persistent organic pollutants in the placenta with the risk of neural tube defects

“…Studies have shown that PAHs and organochlorine pesticides could induce oxidative stress (29)(30)(31)(32)(33). Oxidative stress has long been considered to be a mechanism of teratogenic action for many compounds, resulting in the misregulation of redox-sensitive signal transduction pathways.…”

Prenatal Exposure to Air Pollution, Maternal Psychological Distress, and Child Behavior

“…19,20 Laboratory studies in experimental animals have revealed neurodevelopmental and behavioral effects of PAH exposure during the prenatal and neonatal periods, including anxiety, depressionlike symptoms, and memory impairment. [20][21][22][23][24][25][26] Our previous research in a New York City birth cohort and in the present Krakow birth cohort revealed that prenatal exposure to PAH was associated with adverse cognitive outcomes at age 5 years 27,28 and with behavioral problems, including anxiety and depression, at ages 6 to 7 years in New York City. 29 Although there is some previous human evidence of interactions between socioeconomic factors and pollutants, [30][31][32][33][34] this is the first study assessing the interaction of PAHs and maternal psychological distress on neurobehavioral outcomes.…”

Effects of melatonin on lipid peroxidation and antioxidative enzyme activities in the liver, kidneys and brain of rats administered with benzo(a)pyrene

“…The brain is also characterized by relatively low levels of anti-oxidative enzymes (Reiter, 1995;Escames et al, 1997;Esparza et al, 2005). Moreover, both investigated substances: exogenous melatonin and B(a)P readily cross a blood-brain barrier and reach the brain in a clinical relevant concentrations (Menendez-Pelaez et al, 1993;Moir et al, 1998;Saunders et al, 2006;Reiter et al, 2008;Zhang et al, 2008). The liver was included because of its multiple detoxication pathway including during B(a)P intoxication.…”

“…B(a)P crosses a blood-brain barrier and induces acute neurobehavioral toxicity through oxidative stress due to inhibition of the brain antioxidant scavenging system (Moir et al 1998;Saunders et al, 2006;Zhang et al, 2008). Generation of oxygen-based reactive molecules in brain can increase permeability of the blood-brain barrier and modify synaptic transmission (Evans, 1995).…”