Styrene Metabolism and Striatal Dopamine Depletion in Rabbits

Mutti, Antonio; Romanelli, Alessandro; Falzoi, M; Lucertini, S.; Franchini, I

doi:10.1007/978-3-642-69928-3_101

Cited by 24 publications

(3 citation statements)

References 6 publications

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“…17 18 The styrene metabolites PGA and phenylglycine (the latter is formed by amination of PGA) mimic the effects of styrene on dopamine levels. 25 Mutti and coworkers hypothesised that phenylglycine may compete with dopamine for reuptake into the nerve terminal, increasing the dopamine available for breakdown and decreasing tuberoinfundibular dopamine levels. 17 25 This hypothesised mechanism would predict a rapid effect of styrene exposure on PRL secretion because no DNA transcription or protein synthesis is required and because styrene metabolism to PGA occurs rapidly.…”

Section: Discussionmentioning

confidence: 99%

Temporal association between serum prolactin concentration and exposure to styrene

Luderer

Tornero‐Velez²,

Shay

et al. 2004

Occup Environ Med

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Background: Previous studies have suggested that occupational exposure to styrene is associated with increased serum levels of the anterior pituitary hormone prolactin (PRL). Aims: To test the hypotheses that: (1) the effect of styrene exposure on PRL secretion is an acute effect, not a subchronic or chronic effect; (2) blood styrene, as a measure of absorbed dose, is a stronger predictor of serum PRL level than personal breathing zone air styrene concentration. Methods: Subjects were recruited from 17 workplaces in the reinforced plastics industry. Personal breathing zone air styrene, whole blood styrene, and serum PRL were measured during one to three sessions, approximately one year apart. Linear multiple regression was used to model the relations between acute (air styrene or blood styrene obtained at same time as PRL), subchronic (average air or blood styrene over two or three sessions), and chronic (years of work in industry or facility times average air styrene over all sessions) indices of styrene exposure and serum PRL. Results: Acute blood styrene concentration was the strongest predictor of serum PRL concentration, with the model predicting a 2.06-fold increase in PRL (95% CI 1.11 to 3.84) for every 10-fold increase in blood styrene. Serum PRL tended to increase with increasing styrene exposure in both men and women; however, women tended to have higher PRL levels. For women, the change in blood styrene between sessions 1 and 2 was a significant predictor of the change in serum PRL between sessions. Conclusions: Results confirm that styrene exposure enhances serum PRL concentrations and support an acute effect of styrene on PRL secretion.

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Section: Discussionmentioning

confidence: 99%

Temporal association between serum prolactin concentration and exposure to styrene

Luderer

Tornero‐Velez²,

Shay

et al. 2004

Occup Environ Med

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“…36 The reversibility of transamination reaction partly explains the recovery of dopamine concentrations during the subsequent weeks after depletion caused by styrene exposure. 28 The direction of this reaction might depend on local relative concentrations of exogenous ketoacids and nitrogen donors such as glutamine and glycine.…”

Section: Discussionmentioning

confidence: 99%

Effects of some monocyclic aromatic solvents and their metabolites on brain dopamine in rabbits

Romanelli

Fatzol

Mutti

et al. 1986

J of Applied Toxicology

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Adult male rabbits were exposed to high concentrations (750 ppm, 12 hours daily for 7 days) of toluene, xylenes, styrene, ethylbenzene, vinyltoluene (3-methylstyrene), and 7-methyl-styrene vapours or were dosed with 4 mM/kg/day i.p. of hippuric, methylhippuric, mandelic, phenylglyoxylic, and 7-methyl-mandelic acids. Styrene, vinyltoluene and ethylbenzene caused a marked depletion of striatal and tuberoinfundibular dopamine. Such an effect was also caused by treatment with phenylglyoxylic and mandelic acids. Dopamine depletion was associated with an increase in homovanillic acid concentration in the same regions. These results indicate that dopamine metabolism is a target for the neurotoxic effects of some monocyclic aromatic hydrocarbons and their metabolites, a lateral vinyl- or ethyl-chain being crucial for the structure/activity relationship of such compounds.

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“…Based on the dopaminergic regulation of PRL release and slightly elevated PRL levels measured in occupationally styreneexposed workers, Mutti's group conducted experiments with rabbits (Mutti et al 1984(Mutti et al , 1985, and reported that a 3-or 7-day exposure of the animals to styrene reduced hypothalamic DA concentrations. These observations were also made in the corpus striatum, an extrahypothalamic, DA containing, brain region in which locomotor function is controlled.…”

Section: Introductionmentioning

confidence: 99%

Effects of 5-day styrene inhalation on serum prolactin and dopamine levels and on hypothalamic and striatal catecholamine concentrations in male rats

Jarry¹,

Metten²,

Gamer³

et al. 2002

Archives of Toxicology

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In several studies a hypersecretion of the pituitary hormone prolactin (PRL) in styrene-exposed workers has been described. This should cause reproductive problems like oligomenorrhea, secondary amenorrhea and reduced fertility [Arfini et al. (1987) J Occup Med 29:826-830, Bergamaschi et al. (1996) Neurotoxicology 17:753-760, Mutti and Smargiassi (1998) Toxicol Ind Health 14:311-323]. Secretion of PRL is tonically inhibited by the catecholamine dopamine (DA), which is released from hypothalamic neurons. It has been suggested that the activity of the enzyme dopamine-beta-hydroxylase (DBH) in the serum is a peripheral marker of central dopaminergic function. A slight reduction of such enzymatic activity was observed in styrene-exposed workers, which was associated with hypersecretion of PRL. To further investigate the putative effects of styrene on PRL release, male rats were exposed to styrene vapors (645, 2150 and 6450 mg/m(3)) for 6 h/day on 5 consecutive days. Animals were killed either directly following the last exposure (immediate group) or after a recovery period of 24 h (recovery group). Serum PRL and DA levels were measured by radioimmunoassay. Concentrations of catecholamines and their metabolites in the striatum and mediobasal hypothalamus (MBH) were determined by high performance liquid chromatography with electrochemical detection. Neither in the immediate nor in the recovery group were any statistically significant changes of serum PRL levels observed. Likewise, concentrations of catecholamines and their metabolites in the striatum and MBH remained unaffected. We conclude from these data that styrene, even at very high concentrations, has no adverse effects on the neuroendocrine mechanisms regulating PRL release and DA levels in the brain. With the limitations inherent in any animal model, we suggest that our data indicate that styrene also has no adverse neuroendocrine effects in humans.

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Styrene Metabolism and Striatal Dopamine Depletion in Rabbits

Cited by 24 publications

References 6 publications

Temporal association between serum prolactin concentration and exposure to styrene

Temporal association between serum prolactin concentration and exposure to styrene

Effects of some monocyclic aromatic solvents and their metabolites on brain dopamine in rabbits

Effects of 5-day styrene inhalation on serum prolactin and dopamine levels and on hypothalamic and striatal catecholamine concentrations in male rats

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