Benzo(a)pyrene-induced acute neurotoxicity in the F-344 rat: role of oxidative stress.
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.
Saunders
Crystal R
CR
Department of Pharmacology, Meharry Medical College, Nashville, TN 37208, USA.
Das
Salil K
SK
Ramesh
Aramandla
A
Shockley
Dolores C
DC
Mukherjee
Shyamali
S
D000818:Animals; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D009043:Motor Activity; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D011916:Rats, Inbred F344; D013482:Superoxide Dismutase / Q000378:metabolism
D004785:Environmental Pollutants; D001564:Benzo(a)pyrene; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase