Effects of a unilateral stereotaxic injection of Tinuvin 123 into the substantia nigra on the nigrostriatal dopaminergic pathway in the rat

Tinuvin 123, a compound used in the manufacture of plastics, has recently b een suggested to possibly cause Parkinsons disease (PD). Herein, we revisit ed this issue by assessing the effect of Tinuvin 123 on dopaminergic neuron s of the substantia nigra following its stereotaxic injection in the rat. T wenty-one days post unilateral stereotaxic injection of Tinuvin 123, system ic injection of both apomorphine and amphetamine caused rotations toward th e side of the lesion in these rats. Tinuvin 123 produced a small to moderat e dose-dependent reduction in striatal levels of dopamine and metabolites o n the side of the lesion. This compound also produced dramatic cell loss in the substantia nigra on the side of the lesion. However, the loss of cells lacked the phenotypic specificity for tyrosine hydroxylase (TH)-positive n eurons that is expected with a dopaminergic neurotoxin. Indeed, aside from a robust glial reaction, both TH-positive and glutamic acid dehydrogenase ( GAD)-positive neurons were destroyed, and near the site of the injection, t here was complete tissue destruction. This study indicates that, using this mode of injection, Tinuvin 123 exerts a dramatic tissue toxicity without a ny evidence of specificity for dopaminergic neurons. Thus, our data argues against a role for Tinuvin 123 as an environmental toxin causing a clinical condition characterized by the selective loss of dopaminergic neurons as s een in PD. (C) 2000 Elsevier Science B.V. All rights reserved.