The styrene metabolite, phenylglyoxylic acid, induces striatal-motor toxicity in the rat: influence of dose escalation/reduction over time.

Gisella Terre'Blanche, Nicolette Heyer, Jacobus J Bergh, Lodewyk J Mienie, Cornelius J van der Schyf, Brian H Harvey

Pharmaceutical Chemistry, Unit for Drug Research and Development, School of Pharmacy, North-West University, Private Bag X6001, Box 304, Potchefstroom 2520, South Africa. Gisella.TerreBlanche@nwu.ac.za

Neurotoxicity research 2011 Jul

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Exposure to the industrial solvent, styrene, induces locomotor and cognitive dysfunction in rats, and parkinsonian-like manifestations in man. The antipsychotic, haloperidol (HP), well known to induce striatal toxicity in man and animals, and styrene share a common metabolic pathway yielding p-fluoro phenylglyoxylic acid and phenylglyoxylic acid (PGA), respectively. Using an exposure period of 30 days and the vacous chewing movement (VCM) model as an expression of striatal-motor toxicity, we found that incremental PGA dosing (220-400 mg/kg) significantly increased VCMs up to day 25, but decreased to control levels shortly after reaching maximum dose. However, a diminishing dose of PGA (400-200 mg/kg) did not evoke an immediate worsening of VCMs but precipitated a significant increase in VCMs following dosage reduction to 200 mg/kg on day 22. PGA exposure, therefore, compromises striatal-motor function that is especially sensitive to changes in exposure dose. Longer alternating dose exposure studies are needed to establish whether motor dysfunction is progressive in severity or longevity. These findings are of significance for the environmental toxicology of styrene in the chemical industry.

Citation

Gisella Terre'Blanche, Nicolette Heyer, Jacobus J Bergh, Lodewyk J Mienie, Cornelius J van der Schyf, Brian H Harvey. The styrene metabolite, phenylglyoxylic acid, induces striatal-motor toxicity in the rat: influence of dose escalation/reduction over time. Neurotoxicity research. 2011 Jul;20(1):97-101