Brain dopamine as a target for solvent toxicity: effects of some monocyclic aromatic hydrocarbons.
Adult male rabbits were exposed to toluene, xylene, styrene, ethylbenzene, vinyltoluene or were dosed with hippuric, methylhippuric, mandelic, phenylglyoxylic, and 7-methyl-mandelic acids. Styrene, vinyltoluene and ethylbenzene caused a marked depletion of striatal and tubero-infundibular dopamine. Such an effect was also caused by treatment with mandelic and phenylglyoxylic acids. These results indicate that dopamine is a target for some solvents of their metabolites, the presence of a lateral vinyl- or ethyl-chain which may be biotransformed into alpha-keto acids being crucial for the effect. Experiments in vitro suggest that dopamine condenses non-enzymatically with reactive carbonylic groups of such and other alpha-keto acids, thus becoming ineffective as neurotransmitter. This mechanism might account for the neurobehavioral and neuroendocrine changes which have been reported in workers occupationally exposed to styrene and to some solvent mixtures.
Mutti
A
A
Institute of Clinical Medicine and Nephrology, Chair of Occupational Medicine, University of Parma, Italy.
Falzoi
M
M
Romanelli
A
A
Bocchi
M C
MC
Ferroni
C
C
Franchini
I
I
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D012997:Solvents / Q000633:toxicity*; D020058:Styrene; D013343:Styrenes / Q000633:toxicity*
D012997:Solvents; D013343:Styrenes; D020058:Styrene; D004298:Dopamine; D009638:Norepinephrine