4.7 Article

Association between the levels of biogenic amines and superoxide anion production in brain regions of rats after subchronic exposure to TCDD

Journal

TOXICOLOGY
Volume 228, Issue 2-3, Pages 291-298

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2006.09.009

Keywords

TCDD; brain; cerebellum; brain stem; cerebral cortex; hippocampus; subchronic toxicity; superoxide anion; biogenic amines; HPLC

Funding

  1. NIEHS NIH HHS [R15 ES011048-01, 1 R15 ES11048-01, R15 ES011048] Funding Source: Medline

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The effects of TCDD on the distribution of biogenic amines and production of superoxide anion (SA) in different brain regions of rats have been studied after subchronic exposure. Groups of females Sprague-Dawley rats were administered daily dose of 46 ng TCDD/(kg day) (treated groups), or the vehicle used to dissolve TCDD (control group), for 90 days. The rats were sacrificed at the end of the exposure period and their brains were dissected into different regions including, hippocampus (H), cerebral conex (Cc), cerebellum (C), and brain stem (Bs). The levels of different biogenic amines and some of their metabolites, including, norepinephrine (NE), dopamine (DA), 3,4-dihydroxy phenyl acetic acid (DOPAC), 4-hydroxy-3-methoxy-phenyl acetic acid (HVA), 5-hydroxy tryptamine (5-HT), and 5-hydroxy indole 3-acetic acid (5-HIAA), were determined in those brain regions, using a high performance liquid chromatography (HPLC) system with an electrochemical detector. SA production was also determined in those regions, using the cytochrome c reduction method. Results of analyses indicate significant increases in the levels of DA, NE and DOPAC in H, NE and HVA in Cc, NE and DA in Bs and NE in C. SA production was significantly increased in H and Cc, but not in Bs or C. The results also indicated strong correlations between DA and DOPAC, and SA and NE in all of the brain regions, and also between SA and 5-HT/HIAA in H and Cc. These results may indicate the contribution of biogenic amines, especially NE and 5-HT/HIAA to SA overproduction in some brain regions and may also indicate the potential of long term neurotoxic effects of those biogenic amines, in response to subchronic exposure to TCDD. (c) 2006 Elsevier Ireland Ltd. All riahts reserved.

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