Behavioral effects induced by acute exposure to benzo(a)pyrene in F-344 rats

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are highly persistent environmental pollutants which pose potential adverse effects on human health. Benzo(a)-pyrene (B(a)P) is the prototypical representative of these widely dispersed lipophylic contaminants. (B(a)P) exposure in experimental animals results in an array of tissue- and organ-specific responses including carcinogenicity, teratogenicity, reproductive and immunotoxicity. However, no previous studies have examined the potential neurobehavioral toxicity of B(a)P in vivo. The present study was conducted to investigate the behavioral effects induced by single oral doses of (B(a)P) in 8-week-old male and female F-344 rats. Rats were exposed to 0, 12.5, 25, 50, 100 and 200 mg/kg of B(a)P by oral gavage. Motor activity measurements and the functional observational battery (FOB) were used to assess behavioral changes induced by B(a)P at 2, 4, 6, 8, 10, 12, 24, 48, 72 and 96 h post treatment. Statistical analyses revealed significant (p <0.001) dose, sex and time interactions. (B(a)P) doses ranging from 25 to 200 mg/kg produced a significant suppression (up to 60%) in four motor activity parameters: horizontal activity, total distance, stereotype and vertical activity in both sexes within 2 and 4h of dosing. B(a)P treated male and female animals also showed significant (p <0.001) changes in neuromuscular, autonomic, sensorimotor and physiological functions within 2 and 4h post B(a)P administration except in the 12.5 mg/kg treatment group. The 12.5 mg/kg dose did not produce significant (p > 0.05) behavioral toxicity in either males or females. All treated animals (25-200 mg/kg) recovered from the toxic effects of B(a)P by 72 h. Significant (p < 0.05) gender differences were noted in FOB test measures with males displaying greater sensitivity to B(a)P. These data suggest that motor activity and FOB measurements can be used as indices to detect B(a)P neurotoxicity.

New candidate proteins for Benzo(a)pyrene-induced spatial learning and memory deficits

“…B(a)P is known to affect the central nervous system (CNS), and it has been shown to induce subtle behav- ioral abnormalities, represented mainly by LM deficits (Grova et al, 2007;Saunders et al, 2001Saunders et al, , 2002. Nevertheless, for a complete risk assessment, long-term animal exposure to B(a)P is essential.…”

Comparative Metabolism, Bioavailability, and Toxicokinetics of Benzo[ a ]pyrene in Rats After Acute Oral, Inhalation, and Intravenous Administration

“…Some of these toxic effects include decreases in red blood cells, hemoglobin, white blood cells (10), and neurotoxic effects such as suppression of motor activity (11) and modulation of transcription factors in brain tissue (4).…”

Adverse effect of sub-chronic exposure to benzo(a)pyrene and protective effect of butylated hydroxyanisole on learning and memory ability in male Sprague-Dawley rat

“…The neurotoxic effects of B(a)P have been studied for decades and the mechanism of its toxic effect in the brain is researched in many previous studies (Saunders et al, 2001;Wormley et al, 2004;Niu et al, 2010). One of the mechanisms studied is the relationship between the neurotoxic effect of B(a)P and the hippocampus, which is a particularly vulnerable and sensitive region of the brain.…”