| 1. |
- Mariussen, Espen, et al.
(författare)
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Effect of Polychlorinated Biphenyls on the Uptake of Dopamine into Rat Brain Synaptic Vesicles: A Structure–Activity Study
- 2001
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X. ; 175:2, s. 176-83
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Tidskriftsartikel (refereegranskat)abstract
- PCBs are neurotoxic compounds that have a known effect on the dopaminergic system in the brain. In a previous work it was established that PCBs are potent inhibitors of the uptake of dopamine into rat brain synaptic vesicles. In this work we further investigated the vesicular dopamine uptake in response to different PCBs to explore the structure–activity relationship involved in this effect. Twenty PCB congeners were selected, based on multivariate chemical characterization, to cover the chemical variation within tetra- to hepta-chlorinated PCBs. PCBs of large structural variation were tested and the general finding was that only the ortho-substituted PCBs inhibited the dopamine uptake. The most active congeners were the penta- and hexa-chlorinated PCBs. Furthermore, the uptake was correlated with parameters describing the absolute hardness, the octanol–water partition coefficient, and the Henry's law constant. These parameters are correlated to the number of chlorine atoms in ortho positions and to the size of the molecule. Notably the most active PCBs are highly prevalent in the environment and are disposed to bioaccumulate in wildlife. Thus, these neurotoxic effects should be included in the risk assessment of PCBs.
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| 2. |
- Mariussen, Espen, et al.
(författare)
-
The effect of various substituents in ortho position of biphenyls on respiratory burst, intracellular calcium elevation in human granulocytes, and uptake of dopamine into rat brain synaptic vesicles and synaptosomes
- 2003
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Ingår i: Environmental Toxicology and Pharmacology. ; 14:1-2, s. 43-50
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Tidskriftsartikel (refereegranskat)abstract
- Polychlorinated biphenyls (PCBs) are a group of compounds, which have effects on the immune and nervous system. We have investigated the effects of seven diortho-substituted biphenyls with different substituents on activation of respiratory burst and calcium elevation in human granulocytes, and inhibition of the uptake of dopamine into synaptic vesicles and synaptosomes isolated from rat brain. We have attempted to find the chemical and physical properties, which can contribute to the variation in biological effects. These properties include the absolute hardness, the molecular size, the hydrophobicity of the molecules, the retention time on a DB5-MS GC-column and the electronegativity of the substituents. In general the dichloro- and dibromobiphenyls were the most potent in all biological tests. The difluorosubstituted was less potent than the other two halide-biphenyls presumably because of the smaller size of the substituent. Dimethylbiphenyl was active in all tests. Dihydroxy- and dimethanolbiphenyl were inactive in all tests, whereas dinitrobiphenyl was only active as a vesicular dopamine uptake inhibitor. Important physico-chemical parameters correlated to the effects were absolute hardness, molecular size and lipophilicity. Among the tested diortho-substituted biphenyls the most active were the chlorinated, brominated, and methylated. This indicates the significance of the molecular size in combination with the hydrophobicity for the studied toxic effects.
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